Objective:To investigate the cardioprotective potential of betulin in isoproterenol(ISO)-induced myocardial injury in rats.Methods:Wistar rats were divided into five groups(n=10):normal,ISO,nebivolol 5 mg/kg,and betul...Objective:To investigate the cardioprotective potential of betulin in isoproterenol(ISO)-induced myocardial injury in rats.Methods:Wistar rats were divided into five groups(n=10):normal,ISO,nebivolol 5 mg/kg,and betulin(20&40 mg/kg).Nebivolol and betulin were administered orally for 29 days.ISO(85 mg/kg)was administered subcutaneously on day 27 and day 28 to induce myocardial injury.On day 29,blood was collected for determination of cardiac markers,and hemodynamic parameters were investigated.The levels of oxidative stress markers and the gene expressions of apoptotic markers and inflammatory mediators were evaluated.Moreover,2,3,5-triphenyltetrazolium chloride staining and histopathological analysis were also performed.Results:Betulin reduced the size of myocardial infarction,decreased elevated levels of cardiac enzymes,and maintained hemodynamic functions.It also inhibited ISO-induced upregulation of Bax,caspase-3,NF-κB,and IL-6,enhanced endogenous antioxidant enzymes,and reduced lipid peroxidation.Additionally,pretreatment with betulin alleviated myocardial ischemic damage,as reflected by reduced myonecrosis,edema,and inflammatory changes.Conclusions:Betulin exhibits strong cardioprotective activity against ISO-induced myocardial injury by anti-inflammatory,anti-apoptotic,and antioxidant activities.展开更多
The objective of this work was to investigate the mechanism of action of Balanophora involucrata polyphenolic compounds in the treatment of myocardial injury.In the present study,Balanophora involucrata was extracted ...The objective of this work was to investigate the mechanism of action of Balanophora involucrata polyphenolic compounds in the treatment of myocardial injury.In the present study,Balanophora involucrata was extracted by refluxing 75%of ethanol.The obtained extract was extracted with petroleum ether,ethyl acetate and n-butanol respectively.And the ethyl acetate layer was separated.The extract was prepared by silica gel column chromatography,sephadex LH-20 elution and thin layer chromatography.After that,the Swiss target prediction database was utilized to obtain the targets of Balanophora involucrata,and the Genecards,OMIM and TTD databases were used to predict and screen the targets of Balanophora involucrata for the treatment of myocardial injury.The active ingredient-target network was constructed using Cytoscape software,and the PPI network was mapped using String database and Cytoscape software.GO bioprocess enrichment analysis and KEGG pathway enrichment analysis were performed by Metascape software to predict the mechanism of action.Molecular docking was performed in Discovery Studio 2016 client software to verify the binding of Balanophora involucrata polyphenols to key targets.In this study,six polyphenolic compounds were isolated from Balanophora involucrata.By GO enrichment analysis,1614 biological processes(BP),127 cellular compositions(CC),and 215 molecular functions(MF)were obtained;a total of 155 cross-targets were involved in the KEGG enrichment analysis.The PPI network showed that quercetin was the main active component of polyphenolic compounds against myocardial injury and that AKT1,EGFR,STAT3,SRC,ESR1,MMP9,HSP90AA1 and other related signals were associated with myocardial injury treatment.Finally,the multi-component-multi-target-multi-pathway action of Balanophora involucrata was concluded,which provided new ideas and methods for further research on the mechanism of action of Balanophora involucrata in myocardial injury.展开更多
Objective:To explore the therapeutic efficacy of L-carvone from Mentha spicata L.leaf extracts against isoproterenol-induced cardiac hypertrophy in rats.Methods:Isoproterenol(5 mg/kg)was injected intraperitoneally int...Objective:To explore the therapeutic efficacy of L-carvone from Mentha spicata L.leaf extracts against isoproterenol-induced cardiac hypertrophy in rats.Methods:Isoproterenol(5 mg/kg)was injected intraperitoneally into rats for one month to induce cardiac hypertrophy.L-carvone(25 and 100 mg/kg)was administered orally to treat cardiac hypertrophy.The cardioprotective activity of L-carvone was evaluated by electrocardiogram,histopathological analysis as well as determination of biochemical parameters and enzymatic markers.Results:L-carvone from Mentha spicata L.at 25 and 100 mg/kg ameliorated isoproterenol-induced cardiac hypertrophy,as evidenced by reduced QRS interval on electrocardiogram,and decreased heart weight and heart index.In addition,both doses of L-carvone markedly lowered the levels of glucose,total protein,low-density lipoprotein cholesterol,aspartate transaminase,alanine transaminase,lactate dehydrogenase,creatine kinase MB,troponin-Ⅰ,N-terminal pro-B type natriuretic peptide and triglycerides while increasing high-density lipoprotein cholesterol and lipase level(P<0.05).Moreover,L-carvone alleviated contraction band necrosis,and reorganized the myofibrils with normal striations and myocytes as well as normal nuclei in cardiac histoarchitecture of rats with isoproterenol-induced cardiac hypertrophy.Conclusions:L-carvone from Mentha spicata L.leaf extract can restore abnormal cardiac function and may be further explored as a therapeutic agent against the deleterious effects of cardiac hypertrophy after further evaluation.展开更多
Objective:To explore the effect of continuous non-invasive blood pressure monitoring on intraoperative hemodynamics and postoperative myocardial injury in craniotomy.Methods:120 cases of elective craniotomy were divid...Objective:To explore the effect of continuous non-invasive blood pressure monitoring on intraoperative hemodynamics and postoperative myocardial injury in craniotomy.Methods:120 cases of elective craniotomy were divided into the self-control group(continuous non-invasive blood pressure monitoring and intermittent cuff non-invasive blood pressure monitoring,CNAP group)and propensity score matching group(only intermittent cuff non-invasive blood pressure measurement in previous craniotomy,PSM group);Goal-directed hemodynamic management in CNAP group included heart rate(HR),blood pressure(BP),stroke volume(SV),stroke variability(SVV),and systemic vascular resistance index(SVRI).The main index is to compare the troponin level within 72 hours after operation between the CNAP group and the PSM group;The secondary indicators are the comparison of the hemodynamic conditions between the CNAP group and the PSM at 10 specific time points.Results:The incidence of postoperative myocardial injury in the CNAP group was significantly lower than that in the PSM group(12%vs.30%,P=0.01);in the CNAP group hypotensive episodes(6 vs.3,P=0.01),positive balance of fluid therapy(700 vs.500 mL,P<0.001),more use of vasoactive drugs(29 vs.18,P=0.04),more stable hemodynamics medical status(P=0.03)were recorded.Conclusion:The hemodynamic management strategy based on continuous non-invasive blood pressure monitoring can reduce the incidence of myocardial injury after elective craniotomy and maintain a more stable hemodynamic state.展开更多
Cardiac troponin-I (cTnI) and -T (cTnT) are sensitive and specific markers of myocardial injury. However, the role of increased cTnI and cTnT in percutaneous coronary intervention (PCI)-related myocardial injury...Cardiac troponin-I (cTnI) and -T (cTnT) are sensitive and specific markers of myocardial injury. However, the role of increased cTnI and cTnT in percutaneous coronary intervention (PCI)-related myocardial injury remains controversial. In this prospective, single-center and double-blind study, we aimed to determine the diagnostic and prognostic value of cTnI as well as cTnT (cTns) in PCI-related myocardial injury in a Chinese population. A total of 1,008 patients with stable angina pectoris and non-ST-segment elevation acute coronary syndrome were recruited. The levels of cTnI and cTnT were examined before and after PCI. All patients were followed up for 26± 9 months to observe the incidence of major adverse cardiac events (MACEs). Our results showed that post- PCI cTnI and/or cTnT levels were increased to more than the 99^th percentile upper reference limit (URL) in 133 (13.2%) patients, among which 22 (2.2%) were more than 5 × 99^th percentile URL. By univariate analysis, an elevation in cTns after PCI was not an independent predictor of increased MACEs, HR 1.35 (P = 0.33, 95% CI: 0.74-2.46). In conclusion, our data demonstrate that the incidence of PCI-related myocardial injury is not common in a Chinese population and minor elevated cTns levels may not be a sensitive prognostic marker for MACEs.展开更多
BACKGROUND Abdominal paracentesis drainage(APD)is a safe and effective strategy for severe acute pancreatitis(SAP)patients.However,the effects of APD treatment on SAPassociated cardiac injury remain unknown.AIM To inv...BACKGROUND Abdominal paracentesis drainage(APD)is a safe and effective strategy for severe acute pancreatitis(SAP)patients.However,the effects of APD treatment on SAPassociated cardiac injury remain unknown.AIM To investigate the protective effects of APD on SAP-associated cardiac injury and the underlying mechanisms.METHODS SAP was induced by 5%sodium taurocholate retrograde injection in Sprague-Dawley rats.APD was performed by inserting a drainage tube with a vacuum ball into the lower right abdomen of the rats immediately after SAP induction.Morphological staining,serum amylase and inflammatory mediators,serum and ascites high mobility group box(HMGB)1,cardiac-related enzymes indexes and cardiac function,oxidative stress markers and apoptosis and associated proteins were assessed in the myocardium in SAP rats.Nicotinamide adenine dinucleotide phosphate oxidase activity and mRNA and protein expression were also examined.RESULTS APD treatment improved cardiac morphological changes,inhibited cardiac dysfunction,decreased cardiac enzymes and reduced cardiomyocyte apoptosis,proapoptotic Bax and cleaved caspase-3 protein levels.APD significantly decreased serum levels of HMGB1,inhibited nicotinamide adenine dinucleotide phosphate oxidase expression and ultimately alleviated cardiac oxidative injury.Furthermore,the activation of cardiac nicotinamide adenine dinucleotide phosphate oxidase by pancreatitis-associated ascitic fluid intraperitoneal injection was effectively inhibited by adding anti-HMGB1 neutralizing antibody in rats with mild acute pancreatitis.CONCLUSION APD treatment could exert cardioprotective effects on SAP-associated cardiac injury through suppressing HMGB1-mediated oxidative stress,which may be a novel mechanism behind the effectiveness of APD on SAP.展开更多
BACKGROUND:Sepsis-induced myocardial injury is one of the major predictors of morbidity and mortality of sepsis.The cytoprotective function of erythropoietin(EPO) has been discovered and extensively studied.However,th...BACKGROUND:Sepsis-induced myocardial injury is one of the major predictors of morbidity and mortality of sepsis.The cytoprotective function of erythropoietin(EPO) has been discovered and extensively studied.However,the cardioprotective effects of EPO on sepsis-induced myocardial injury in the rat sepsis model has not been reported.METHODS:The rat models of sepsis were produced by cecal ligation and perforation(CLP)surgery.Rats were randomly(random number) assigned to one of three groups(n=8 for each group):sham group,CLP group and EPO group(1000 lU/kg erythropoietin).Arterial blood was withdrawn at3,6,12,and 24 hours after CLP.cTnl,BNP,CK-MB,LDH,AST,TNF-a,IL-6,IL-10,and CRP were tested by the ELISA assay.Changes of hemodynamic parameters were recorded at 3,6,12,24 hours after the surgery.Histological diagnosis was made by hematoxylin and eosin.Flow cytometry was performed to examine cell apoptosis,myocardium mitochondrial inner membrane potential,and NF-κB(p65).Survival rate at 7 days after CLP was recorded.RESULTS:In the CLP group,myocardial enzyme index and inflammatory index increased at3,6,12 and 24 hours after CLP compared with the sham group,and EPO significantly blocked the increase.Compared with the CLP group,EPO significantly improved LVSP,LV +dpldt_(max) LV-dp/dt_(min),and decreased LVEDP at different time.EPO blocked the reduction of mitochondrial transmembrane potential,suppressed the cardiomyocyte apoptosis,inhibited the activation of NF-κB,and reduced the production of proinflmmatory cytokines.No difference in the survival rate at 7 days was observed between the CLP group and the EPO group.CONCLUSION:Exogenous EPO has cardioprotective effects on sepsis-induced myocardial injury.展开更多
Objective:Keshan disease(KD)is a mitochondrial cardiomyopathy.The present study explored the roles of peroxisome proliferator-activated receptor(PPAR)-y coactivator-la(PGC-la),the key regulator of mitochondrial struct...Objective:Keshan disease(KD)is a mitochondrial cardiomyopathy.The present study explored the roles of peroxisome proliferator-activated receptor(PPAR)-y coactivator-la(PGC-la),the key regulator of mitochondrial structure and function,and its coactivators in myocardial injury in chronic KD.Furthermore,the usefulness of these molecules in the diagnosis of chronic KD was assessed.展开更多
Objective To evaluate the effects and mechanisms of glucose-insulin-potassium(GIK)on post-procedural myocardial injury(PMI)after percutaneous coronary intervention(PCI).Methods A total of 200 non-diabetic patients wit...Objective To evaluate the effects and mechanisms of glucose-insulin-potassium(GIK)on post-procedural myocardial injury(PMI)after percutaneous coronary intervention(PCI).Methods A total of 200 non-diabetic patients with documented coronary heart disease(CHD)were divided into the Group GIK and Group G,with 100 patients in each group.Patients in Group G were given intravenous infusion of glucose solution 2 hours before PCI.As compared,patients in Group GIK were given GIK.Results Both post-procedural creatine phosphokinase isoenzyme MB(CK-MB;62.1±47.8 vs.48.8±52.6 U/L,P=0.007)and cTnI(0.68±0.83 vs.0.19±0.24 ng/mL,P<0.001)in Group GIK were significantly higher than those in Group G.In Group G,9.0%and 4.0%of patients had post-procedural increases in CK-MB 1-3 times and>3 times,which were significantly lower than those in Group GIK(14.0%and 7.0%,respectively;all P values<0.01);13.0%and 7.0%of patients had post-procedural increases in cTnI 1-3 times and>3 times,which were also significantly lower than those in Group GIK(21.0%and 13.0%,respectively;all P<0.001).Pre-procedural(10.2±4.5 vs.5.1±6.3,P<0.001)and post-procedural rapid blood glucose(RBG)levels(8.9±3.9 vs.5.3±5.6,P<0.001)in Group G were higher than those in Group GIK.In adjusted logistic models,usage of GIK(compared with glucose solution)remained significantly and independently associated with higher risk of post-procedural increases in both CK-MB and cTnI levels>3 times.Furthermore,pre-procedural RBG levels<5.0mmol/L were significantly associated with higher risk of post-procedural increases in both CK-MB and cTnI levels.Conclusions In non-diabetic patients with CHD,the administration of GIK may increase the risk of PMI due to hypoglycemia induced by GIK.展开更多
Severe acute respiratory syndrome coronavirus 2 infection affects not only the lungs,but also the cardiovascular system,having a major impact on patients’outcomes.Myocardial injury(MI)occurs in the context of coronav...Severe acute respiratory syndrome coronavirus 2 infection affects not only the lungs,but also the cardiovascular system,having a major impact on patients’outcomes.Myocardial injury(MI)occurs in the context of coronavirus infectious disease 2019(COVID-19)and is associated with a higher risk of severe clinical outcome and mortality.COVID-19-related MI can have various clinical manifestations,of which the main ones are myocarditis,stress cardiomyopathy,acute coronary syndrome,and pulmonary embolism.The exact mechanisms of how MI occurs in these patients are not yet fully known.Direct injury,through direct viral myocardial invasion,and indirect injury,through interaction with angiotensin I converting enzyme 2,increased inflammation,and thrombocyte and endothelial dysfunction,could be involved in acute MI in patients with COVID-19.A better understanding of these multiple potential mechanisms may help to develop new targeted therapeutic strategies.The purpose of this review is to provide the current understanding of the potential mechanisms involved in MI induced by COVID-19 and to discuss the current progress in the therapeutic strategies.展开更多
Objective This study aimed to examine the effects of microcirculatory dysfunction and 654-1intervention after cardiopulmonary resuscitation on myocardial injury.Methods Landrace pigs were divided into a sham operation...Objective This study aimed to examine the effects of microcirculatory dysfunction and 654-1intervention after cardiopulmonary resuscitation on myocardial injury.Methods Landrace pigs were divided into a sham operation group(S group,n=6),ventricular fibrillation control group(VF-C group,n=8)and 654-1 intervention group(VF-I group,n=8).Hemodynamics was recorded at baseline,at recovery of spontaneous circulation(ROSC),and 1 h,2 h,4h and 6 h thereafter.Sidestream dark field(SDF)technology was used to evaluate and monitor the microcirculation flow index,total vessel density,perfusion vessel ratio,De-Backer score,and perfusion vessel density in animal viscera at various time points.Results After administration of 654-1 at 1.5 h post-ROSC,the hemodynamics in the VF-I group,as compared with the VF-C group,was significantly improved.The visceral microcirculation detected by SDF was also significantly improved in the VF-I group.As observed through electron microscopy,significantly less myocardial tissue injury was present in the VF-I group than the VF-C group.Conclusion Administration of 654-1 inhibited excessive inflammatory by improving the state of visceral microcirculation.展开更多
Objective:To observe the effect of resveratrol on the injury of diabetic cardiomyocytes and its effect on HSF1 mediated iron death.Methods:the diabetic cardiomyopathy model was established by high glucose induced H9c2...Objective:To observe the effect of resveratrol on the injury of diabetic cardiomyocytes and its effect on HSF1 mediated iron death.Methods:the diabetic cardiomyopathy model was established by high glucose induced H9c2,and H9c2 was exposed to normal glucose concentration as a control.Then the intervention was performed with the corresponding drugs.The cell proliferation level was detected by CCK8 method,the concentrations of LDH,SOD,MDA and iron ions were detected by kit method,and the expression levels of HSF1,apoptotic proteins(Bax and Bcl-2)and iron death marker proteins(ACSL4,GPX4 and SLC7A11)were detected by Western blot;Results:compared with the blank group,the cell activity,SOD activity,the expression of HSF1,Bcl-2,GPX4 and SLC7A11 protein in the model group decreased significantly,and the LDH activity,MDA content,Bax and ACSL4 protein expression,Bax/Bcl-2 ratio and Fe^(2+)content increased significantly(P<0.01).Compared with the model group,the activity of H9c2 cells,the activity of SOD,the expression of HSF1,Bcl-2,GPX4 and SLC7A11 protein increased significantly,and the activity of LDH,the content of MDA,the expression of Bax and ACSL4 protein,the ratio of Bax/Bcl-2 and the content of Fe^(2+)decreased significantly in the resveratrol group(P<0.01).After the intervention,the activity of H9c2 cells,the activity of SOD,the expression of HSF1,Bcl-2,GPX4 and SLC7A11 protein decreased significantly,and the activity of LDH,the content of MDA,the expression of Bax and ACSL4 protein,the ratio of Bax/Bcl-2 and the content of Fe^(2+)increased significantly in si-hsf1 group(P<0.01);Conclusion:resveratrol can inhibit cell iron death and improve high glucose induced cardiomyocyte injury by up regulating the expression of HSF1.展开更多
Objectives To investigate the effect of co-exposure of myocardial ischemia and cold stress on myocardial injury in rats and the relative mechanism.Methods Myocardial ischemia model was established by ligation of left ...Objectives To investigate the effect of co-exposure of myocardial ischemia and cold stress on myocardial injury in rats and the relative mechanism.Methods Myocardial ischemia model was established by ligation of left coronary artery.SD rats were randomly allocated to 4 groups; sham+normal temperature(S group),sham+cold stress(SC group),myocardial ischemia+ normal temperature(Ⅰgroup), myocardial ischemia+cold stress(IC group).On the condition of 26℃,SC and IC groups were keeped in a 4℃artificial chamber for 8h(8;00-16:00) for 4 consecu- tive days.Car diac function was assessed by echocardiography;pathological change was analyzed by HE staining;myocardial infarct size was determined by TTC staining;Bim,Caspase-3 expression in myocardium was determined by western blotting.Results It was demonstrated that co-exposure of myocardial ischemia and cold stress could significantly make the cardiac muscle in abnormal shape,increase the infarct size and the expression of Bim and Caspase-3.Conclusions Co-exposure of myocardial ischemia and cold stress may aggravate the cardiac injury,pro- apoptosis protein Bim is involved.展开更多
Myocardial injury as one of the severe complications leads to the increasing morbidity and mortality in patients with sepsis.Recent studies reported that reactive oxygen species(ROS)-mediated ferroptosis plays a criti...Myocardial injury as one of the severe complications leads to the increasing morbidity and mortality in patients with sepsis.Recent studies reported that reactive oxygen species(ROS)-mediated ferroptosis plays a critical role in the development of heart diseases.Therefore,we hypothesized that anti-ferroptosis agent might be a novel potential therapeutic strategy for sepsis-induced cardiac injury.Herein,we demonstrated that a small biocompatible and MRI-visible melanin nanoparticles(MMPP)improves myocardial function by inhibiting ROS-related ferroptosis signaling pathway.In LPS-induced murine sepsis model,after a single dose intravenously injection of MMPP treatment,MMPP markedly alleviated the myocardial injury including cardiac function and heart structure disorder through suppressing iron-accumulation induced ferroptosis.In vitro,MMPP inhibited cardiomyocyte death by attenuating oxidative stress,inflammation and maintaining mitochondrial homeostasis.Collectively,our findings demonstrated that MMPP protected heart against sepsis-induced myocardial injury via inhibiting ferroptosis and inflammation,which might be a novel therapeutic approach in future.展开更多
Background:Liqi Huoxue dripping pill(LQHXDP),a traditional Chinese drug for coronary heart disease,has a protective effect on the heart of rats with myocardial ischemia-reperfusion injury(MIRI)in previous studies;howe...Background:Liqi Huoxue dripping pill(LQHXDP),a traditional Chinese drug for coronary heart disease,has a protective effect on the heart of rats with myocardial ischemia-reperfusion injury(MIRI)in previous studies;however,its mechanism of action remains unclear.The purpose of this study was to investigate the protective mechanism of LQHXDP on MIRI in rats and its relationship with the PI3K/Akt signaling pathway.Methods:In this study,Sprague-Dawley rats were pre-infused with LQHXDP(175 mg/kg/d)for 10 days.PI3K inhibitor LY294002(0.3 mg/kg)was intravenously injected 15 minutes before ischemia.The rat model of MIRI was established by ligating the left anterior descending coronary artery.Subsequently,cardiac hemodynamics,serum myocardial injury markers,inflammatory factors,myocardial infarct size,antioxidant indexes,myocardial histopathology,and phosphorylation levels of key proteins of PI3K/Akt signaling pathway were assessed in rats.Results:LQHXDP was found to improve cardiac hemodynamic indexes,reduce serum creatine kinase MB isoenzyme activity and cardiac troponin and heart-type fatty acid binding protein levels,lower serum interleukin-1 beta,interleukin-6 and tumour necrosis factorαlevels,reduce the myocardial infarct size and enhance the antioxidant capacity of myocardial tissue in MIRI rats.Pathological analysis revealed that LQHXDP attenuated the extent of myocardial injury and protected mitochondria from damage in MIRI rats.Immunoblot analysis revealed that LQHXDP increased the expression levels of p-Akt and p-GSK-3βin MIRI rat cardiomyocytes.PI3K inhibitor LY294002 could impair these effects of LQHXDP.Conclusion:LQHXDP attenuated myocardial injury,attenuated oxidative stress injury and reduced inflammatory response in MIRI rats,and its protective effects were mediated by activating of PI3K/Akt/GSK-3βsignaling pathway.展开更多
Myocardial injury is one of the most common comorbidity in SARS-CoV-2 infected patients,and has poor prognosis.However,the incidence of myocardial injury in patients with SARS-CoV-2 infection has not been sufficiently...Myocardial injury is one of the most common comorbidity in SARS-CoV-2 infected patients,and has poor prognosis.However,the incidence of myocardial injury in patients with SARS-CoV-2 infection has not been sufficiently investigated during the Omicron wave.We conducted a retrospective study of 2690 patients with confirmed SARS-CoV-2 Omicron infection from Tongji Hospital.The results indicated that the myocardial injury accounted for 30.8%of the total patients with SARS-CoV-2 infection and was associated with higher in-hospital mortality than those without injury before and after propensity score matching(PSM)[adjusted hazard ratio(HR),10.61;95%confidence interval(CI),7.76–14.51;P<0.001;adjusted HR,2.70;95%CI,1.86–3.93;P<0.001;respectively].Further,the levels of cytokines(IL-1β,IL-6,IL-10,and TNF-α)in patients with myocardial injury were higher than those without injury,and the higher levels of cytokines in the myocardial injury group were associated with increased mortality.Administration of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers(ACEI/ARB)could significantly reduce the mortality in patients with myocardial injury(adjusted HR,0.52;95%CI,0.38–0.71;P<0.001).Additionally,the level of angiotensin II increased in patients with SARS-CoV-2 infection was even higher in myocardial injury group compared to those without injury.Collectively,the study summarized the clinical characteristic and outcome of SARS-CoV-2 infected patients with myocardial injury during the Omicron wave in China,and validated the protective role of ACEI/ARB in improving the survival of those with myocardial injury.展开更多
OBJECTIVE:To examine the effects of moxibustion on myocardial injury and myocardial metabolomics in rats with rheumatoid arthritis(RA)based on the transforming growth factor beta1(TGF-β1)/Smads signaling pathway.METH...OBJECTIVE:To examine the effects of moxibustion on myocardial injury and myocardial metabolomics in rats with rheumatoid arthritis(RA)based on the transforming growth factor beta1(TGF-β1)/Smads signaling pathway.METHODS:One hundred rats were treated with saline[normal control(NC)group]or complete Freund’s adjuvant(CFA)by right plantar injection for the RA model group,and the latter were randomly divided into 4 groups.Tripterygium wilfordii polyglycoside tablets(雷公藤多苷片,TPT)have anti-inflammatory and are widely used in the clinical treatment of RA,therefore serving as a positive control group.Three days post injection rats were given TPT tablet(TPT group),acupuncture therapy(APT group),and moxibustion treatment(MOX group)for 15 consecutive days,while NC group and model group were equally grasped and fixed and received normal saline.Rat joint swelling scores and arthritis index(AI)were evaluated in each group before the CFA challenge,therapy and after receiving therapy.Myocardial ultrastructure was observed by electron microscope.Enzyme-linked immunosorbent assay was used to detect cardiac troponin I(cTnI)levels in rat myocardial tissue.Quantitative reverse transcription polymerase chain reaction and Western blotting analysis were used to measure the mRNA and protein levels of TGF-βsignaling molecules including TGF-β1,Smad2,Smad3,Smad4,and Smad7.Myocardial metabolomics was analyzed using gas chromatography-mass spectrometer.RESULTS:Compared with model group,RA model rats receiving TPT,acupuncture,or moxibustion therapy all showed reduced joint swelling scores and AI(all P<0.01)and improved myocardial damage,whereas rats treated with moxibustion were found to be more marked.Consistently,the expressions of cTnI,TGF-β1,Smad2,Smad3,and Smad4 were found to be elevated in model rat group in contrast to NC rats and were significantly downregulated in TPT,APT and MOX group when compared with model group,while the levels of Smad7 showed the opposite result(all P<0.01).Moreover,the dissection of metabolomics suggested a novel metabolite biomarker panel including D-Xylulose 5-phosphate,dihydroxyacetone phosphate,arachidonic acid,etc was defined and implicated in amino acid,glucose,and fatty acid metabolic processes as revealed by principal component analysis and partial least squares discriminant analysis.CONCLUSION:Moxibustion prevents RA-induced inflammatory response and offers potent therapeutic effects on myocardial dysfunctions.The protective effects might be associated with its role in TGF-β1 inactivation and metabolic reprogramming.展开更多
BACKGROUND Patients with diabetes mellitus are at higher risk of myocardial ischemia/reperfusion injury(MI/RI).Shuxin decoction(SXT)is a proven recipe modification from the classic herbal formula"Wu-tou-chi-shi-z...BACKGROUND Patients with diabetes mellitus are at higher risk of myocardial ischemia/reperfusion injury(MI/RI).Shuxin decoction(SXT)is a proven recipe modification from the classic herbal formula"Wu-tou-chi-shi-zhi-wan"according to the traditional Chinese medicine theory.It has been successfully used to alleviate secondary MI/RI in patients with diabetes mellitus in the clinical setting.However,the underlying mechanism is still unclear.AIM To further determine the mechanism of SXT in attenuating MI/RI associated with diabetes.METHODS This paper presents an ensemble model combining network pharmacology and biology.The Traditional Chinese Medicine System Pharmacology Database was accessed to select key components and potential targets of the SXT.In parallel,therapeutic targets associated with MI/RI in patients with diabetes were screened from various databases including Gene Expression Omnibus,DisGeNet,Genecards,Drugbank,OMIM,and PharmGKB.The potential targets of SXT and the therapeutic targets related to MI/RI in patients with diabetes were intersected and subjected to bioinformatics analysis using the Database for Annotation,Visualization and Integrated Discovery.The major results of bioinformatics analysis were subsequently validated by animal experiments.RESULTS According to the hypothesis derived from bioinformatics analysis,SXT could possibly ameliorate lipid metabolism disorders and exert anti-apoptotic effects in MI/RI associated with diabetes by reducing oxidized low density lipoprotein(LDL)and inhibiting the advanced glycation end products(AGE)-receptor for AGE(RAGE)signaling pathway.Subsequent animal experiments confirmed the hypothesis.The treatment with a dose of SXT(2.8 g/kg/d)resulted in a reduction in oxidized LDL,AGEs,and RAGE,and regulated the level of blood lipids.Besides,the expression of apoptosis-related proteins such as Bax and cleaved caspase 3 was down-regulated,whereas Bcl-2 expression was up-regulated.The findings indicated that SXT could inhibit myocardial apoptosis and improve cardiac function in MI/RI in diabetic rats.CONCLUSION This study indicated the active components and underlying molecular therapeutic mechanisms of SXT in MI/RI with diabetes.Moreover,animal experiments verified that SXT could regulate the level of blood lipids,alleviate cardiomyocyte apoptosis,and improve cardiac function through the AGE-RAGE signaling pathway.展开更多
Background:Currently,no drugs can specifically improve clinical cardiac ischemia-reperfusion injury or the prognosis of hemodialysis.Salvianolic acid B(SalB)is a widely used cardiac protectant;however,its clinical app...Background:Currently,no drugs can specifically improve clinical cardiac ischemia-reperfusion injury or the prognosis of hemodialysis.Salvianolic acid B(SalB)is a widely used cardiac protectant;however,its clinical application is limited by its low oral bioavailability and poor intestinal absorption.The exploration of its preparation and clinical applications has become a research hotspot in recent years.Methods:To determine whether mesoporous silica nanoparticles(MSNs)efficiently delivered SalB to the heart and SalB@MSNs-RhB reduced myocardial ischemia-reperfusion injury,we constructed a myocardial ischemia-reperfusion male rat model,hypoxia/reoxygenation cardiomyocytes,and treated them with SalB@MSNs-RhB.Results:SalB@MSNs-RhB showed improved bioavailability,therapeutic effect,heightened JAK2/STAT3-dependent pro-survival signaling,and antioxidant responses,thereby protecting cardiomyocytes from ischemia-reperfusion injury-induced oxidative stress and apoptosis.Conclusion:This use of SalB-loaded nanoparticles and investigation of their mechanism of action may provide a new strategy for treating cardiomyocytes.Thus,hypoxia/reoxygenation promotes the clinical application of SalB.展开更多
Purpose: Ischemia-reperfusion (I/R) injury exacerbates myocardial cell death (including apoptosis and necrosis), leading to complications such as arrhythmias, myocardial stenosis, microvascular obstruction and heart f...Purpose: Ischemia-reperfusion (I/R) injury exacerbates myocardial cell death (including apoptosis and necrosis), leading to complications such as arrhythmias, myocardial stenosis, microvascular obstruction and heart failure, and it is particularly important to seek new strategies to mitigate reperfusion injury. In this paper, we will investigate whether atorvastatin can alleviate myocardial ischemia-reperfusion injury and verify its molecular mechanism. Methods: We successfully constructed a hypoxia-reperfusion (H/R) H9c2 cell model and transfected miR-26a-5p mimic, miR-26a-5p inhibitor and its negative control NC-mimic or NC-inhibitor into H9c2 cells using a transfection kit. The expression of miR-26a-5p and FOXO1 were detected by RT-qPCR assay, the expression of related proteins by Western blot assay, the cell viability of H9c2 cells by CCK-8 assay, the apoptosis rate of H9c2 cells by flow cytometry, the CK and LDH activity in cells by CK and LDH assay kits. The targeting relationship between miR-26a-5p and FOXO1 was verified by dual luciferase reporter gene assay. Results: MiR-26a-5p expression was decreased in H/R-induced cells and FOXO1 expression was increased in H/R-induced cells. Atorvastatin alleviated H/R injury in cardiomyocytes and was most effective at a concentration of 1 μM. Atorvastatin alleviated H/R injury in cardiomyocytes by upregulating miR-26a-5p expression, miR-26a-5p and FOXO1 were negatively regulated by targeting. Conclusion: Atorvastatin can alleviate H/R injury in cardiomyocytes by regulating miR-26a-5p/FOXO1.展开更多
文摘Objective:To investigate the cardioprotective potential of betulin in isoproterenol(ISO)-induced myocardial injury in rats.Methods:Wistar rats were divided into five groups(n=10):normal,ISO,nebivolol 5 mg/kg,and betulin(20&40 mg/kg).Nebivolol and betulin were administered orally for 29 days.ISO(85 mg/kg)was administered subcutaneously on day 27 and day 28 to induce myocardial injury.On day 29,blood was collected for determination of cardiac markers,and hemodynamic parameters were investigated.The levels of oxidative stress markers and the gene expressions of apoptotic markers and inflammatory mediators were evaluated.Moreover,2,3,5-triphenyltetrazolium chloride staining and histopathological analysis were also performed.Results:Betulin reduced the size of myocardial infarction,decreased elevated levels of cardiac enzymes,and maintained hemodynamic functions.It also inhibited ISO-induced upregulation of Bax,caspase-3,NF-κB,and IL-6,enhanced endogenous antioxidant enzymes,and reduced lipid peroxidation.Additionally,pretreatment with betulin alleviated myocardial ischemic damage,as reflected by reduced myonecrosis,edema,and inflammatory changes.Conclusions:Betulin exhibits strong cardioprotective activity against ISO-induced myocardial injury by anti-inflammatory,anti-apoptotic,and antioxidant activities.
基金Project supported by National Training Program of Innovation and Entrepreneurship for Undergraduates(202310163020,S202310163079).
文摘The objective of this work was to investigate the mechanism of action of Balanophora involucrata polyphenolic compounds in the treatment of myocardial injury.In the present study,Balanophora involucrata was extracted by refluxing 75%of ethanol.The obtained extract was extracted with petroleum ether,ethyl acetate and n-butanol respectively.And the ethyl acetate layer was separated.The extract was prepared by silica gel column chromatography,sephadex LH-20 elution and thin layer chromatography.After that,the Swiss target prediction database was utilized to obtain the targets of Balanophora involucrata,and the Genecards,OMIM and TTD databases were used to predict and screen the targets of Balanophora involucrata for the treatment of myocardial injury.The active ingredient-target network was constructed using Cytoscape software,and the PPI network was mapped using String database and Cytoscape software.GO bioprocess enrichment analysis and KEGG pathway enrichment analysis were performed by Metascape software to predict the mechanism of action.Molecular docking was performed in Discovery Studio 2016 client software to verify the binding of Balanophora involucrata polyphenols to key targets.In this study,six polyphenolic compounds were isolated from Balanophora involucrata.By GO enrichment analysis,1614 biological processes(BP),127 cellular compositions(CC),and 215 molecular functions(MF)were obtained;a total of 155 cross-targets were involved in the KEGG enrichment analysis.The PPI network showed that quercetin was the main active component of polyphenolic compounds against myocardial injury and that AKT1,EGFR,STAT3,SRC,ESR1,MMP9,HSP90AA1 and other related signals were associated with myocardial injury treatment.Finally,the multi-component-multi-target-multi-pathway action of Balanophora involucrata was concluded,which provided new ideas and methods for further research on the mechanism of action of Balanophora involucrata in myocardial injury.
文摘Objective:To explore the therapeutic efficacy of L-carvone from Mentha spicata L.leaf extracts against isoproterenol-induced cardiac hypertrophy in rats.Methods:Isoproterenol(5 mg/kg)was injected intraperitoneally into rats for one month to induce cardiac hypertrophy.L-carvone(25 and 100 mg/kg)was administered orally to treat cardiac hypertrophy.The cardioprotective activity of L-carvone was evaluated by electrocardiogram,histopathological analysis as well as determination of biochemical parameters and enzymatic markers.Results:L-carvone from Mentha spicata L.at 25 and 100 mg/kg ameliorated isoproterenol-induced cardiac hypertrophy,as evidenced by reduced QRS interval on electrocardiogram,and decreased heart weight and heart index.In addition,both doses of L-carvone markedly lowered the levels of glucose,total protein,low-density lipoprotein cholesterol,aspartate transaminase,alanine transaminase,lactate dehydrogenase,creatine kinase MB,troponin-Ⅰ,N-terminal pro-B type natriuretic peptide and triglycerides while increasing high-density lipoprotein cholesterol and lipase level(P<0.05).Moreover,L-carvone alleviated contraction band necrosis,and reorganized the myofibrils with normal striations and myocytes as well as normal nuclei in cardiac histoarchitecture of rats with isoproterenol-induced cardiac hypertrophy.Conclusions:L-carvone from Mentha spicata L.leaf extract can restore abnormal cardiac function and may be further explored as a therapeutic agent against the deleterious effects of cardiac hypertrophy after further evaluation.
文摘Objective:To explore the effect of continuous non-invasive blood pressure monitoring on intraoperative hemodynamics and postoperative myocardial injury in craniotomy.Methods:120 cases of elective craniotomy were divided into the self-control group(continuous non-invasive blood pressure monitoring and intermittent cuff non-invasive blood pressure monitoring,CNAP group)and propensity score matching group(only intermittent cuff non-invasive blood pressure measurement in previous craniotomy,PSM group);Goal-directed hemodynamic management in CNAP group included heart rate(HR),blood pressure(BP),stroke volume(SV),stroke variability(SVV),and systemic vascular resistance index(SVRI).The main index is to compare the troponin level within 72 hours after operation between the CNAP group and the PSM group;The secondary indicators are the comparison of the hemodynamic conditions between the CNAP group and the PSM at 10 specific time points.Results:The incidence of postoperative myocardial injury in the CNAP group was significantly lower than that in the PSM group(12%vs.30%,P=0.01);in the CNAP group hypotensive episodes(6 vs.3,P=0.01),positive balance of fluid therapy(700 vs.500 mL,P<0.001),more use of vasoactive drugs(29 vs.18,P=0.04),more stable hemodynamics medical status(P=0.03)were recorded.Conclusion:The hemodynamic management strategy based on continuous non-invasive blood pressure monitoring can reduce the incidence of myocardial injury after elective craniotomy and maintain a more stable hemodynamic state.
基金supported by the Health Bureau of Jiangsu Province(No.K201104)the Scientific Support Plan of Jiangsu Province(No.BE2011803)+2 种基金the National Natural Science Foundation of China(No.81170102/H0203)the Priority Academic Program Development of Jiangsu Higher Education Institutions(No.BL2012011)the Fourth Period Project"333"of Jiangsu Province(No.BRA2012207),China
文摘Cardiac troponin-I (cTnI) and -T (cTnT) are sensitive and specific markers of myocardial injury. However, the role of increased cTnI and cTnT in percutaneous coronary intervention (PCI)-related myocardial injury remains controversial. In this prospective, single-center and double-blind study, we aimed to determine the diagnostic and prognostic value of cTnI as well as cTnT (cTns) in PCI-related myocardial injury in a Chinese population. A total of 1,008 patients with stable angina pectoris and non-ST-segment elevation acute coronary syndrome were recruited. The levels of cTnI and cTnT were examined before and after PCI. All patients were followed up for 26± 9 months to observe the incidence of major adverse cardiac events (MACEs). Our results showed that post- PCI cTnI and/or cTnT levels were increased to more than the 99^th percentile upper reference limit (URL) in 133 (13.2%) patients, among which 22 (2.2%) were more than 5 × 99^th percentile URL. By univariate analysis, an elevation in cTns after PCI was not an independent predictor of increased MACEs, HR 1.35 (P = 0.33, 95% CI: 0.74-2.46). In conclusion, our data demonstrate that the incidence of PCI-related myocardial injury is not common in a Chinese population and minor elevated cTns levels may not be a sensitive prognostic marker for MACEs.
基金Supported by National Natural Science Foundation of China,No.81772001National Clinical Key Subject of China,No.41792113Technology Plan Program of Sichuan Provence,No.2015SZ0229,No.2016HH0067,No.2018JY0041and No.2019YJ0277
文摘BACKGROUND Abdominal paracentesis drainage(APD)is a safe and effective strategy for severe acute pancreatitis(SAP)patients.However,the effects of APD treatment on SAPassociated cardiac injury remain unknown.AIM To investigate the protective effects of APD on SAP-associated cardiac injury and the underlying mechanisms.METHODS SAP was induced by 5%sodium taurocholate retrograde injection in Sprague-Dawley rats.APD was performed by inserting a drainage tube with a vacuum ball into the lower right abdomen of the rats immediately after SAP induction.Morphological staining,serum amylase and inflammatory mediators,serum and ascites high mobility group box(HMGB)1,cardiac-related enzymes indexes and cardiac function,oxidative stress markers and apoptosis and associated proteins were assessed in the myocardium in SAP rats.Nicotinamide adenine dinucleotide phosphate oxidase activity and mRNA and protein expression were also examined.RESULTS APD treatment improved cardiac morphological changes,inhibited cardiac dysfunction,decreased cardiac enzymes and reduced cardiomyocyte apoptosis,proapoptotic Bax and cleaved caspase-3 protein levels.APD significantly decreased serum levels of HMGB1,inhibited nicotinamide adenine dinucleotide phosphate oxidase expression and ultimately alleviated cardiac oxidative injury.Furthermore,the activation of cardiac nicotinamide adenine dinucleotide phosphate oxidase by pancreatitis-associated ascitic fluid intraperitoneal injection was effectively inhibited by adding anti-HMGB1 neutralizing antibody in rats with mild acute pancreatitis.CONCLUSION APD treatment could exert cardioprotective effects on SAP-associated cardiac injury through suppressing HMGB1-mediated oxidative stress,which may be a novel mechanism behind the effectiveness of APD on SAP.
基金supported by a grant from the National Natural Science Foundation of China(81070122)
文摘BACKGROUND:Sepsis-induced myocardial injury is one of the major predictors of morbidity and mortality of sepsis.The cytoprotective function of erythropoietin(EPO) has been discovered and extensively studied.However,the cardioprotective effects of EPO on sepsis-induced myocardial injury in the rat sepsis model has not been reported.METHODS:The rat models of sepsis were produced by cecal ligation and perforation(CLP)surgery.Rats were randomly(random number) assigned to one of three groups(n=8 for each group):sham group,CLP group and EPO group(1000 lU/kg erythropoietin).Arterial blood was withdrawn at3,6,12,and 24 hours after CLP.cTnl,BNP,CK-MB,LDH,AST,TNF-a,IL-6,IL-10,and CRP were tested by the ELISA assay.Changes of hemodynamic parameters were recorded at 3,6,12,24 hours after the surgery.Histological diagnosis was made by hematoxylin and eosin.Flow cytometry was performed to examine cell apoptosis,myocardium mitochondrial inner membrane potential,and NF-κB(p65).Survival rate at 7 days after CLP was recorded.RESULTS:In the CLP group,myocardial enzyme index and inflammatory index increased at3,6,12 and 24 hours after CLP compared with the sham group,and EPO significantly blocked the increase.Compared with the CLP group,EPO significantly improved LVSP,LV +dpldt_(max) LV-dp/dt_(min),and decreased LVEDP at different time.EPO blocked the reduction of mitochondrial transmembrane potential,suppressed the cardiomyocyte apoptosis,inhibited the activation of NF-κB,and reduced the production of proinflmmatory cytokines.No difference in the survival rate at 7 days was observed between the CLP group and the EPO group.CONCLUSION:Exogenous EPO has cardioprotective effects on sepsis-induced myocardial injury.
基金This research was supported by the National Natural Science Foundation of China(No.81402637).
文摘Objective:Keshan disease(KD)is a mitochondrial cardiomyopathy.The present study explored the roles of peroxisome proliferator-activated receptor(PPAR)-y coactivator-la(PGC-la),the key regulator of mitochondrial structure and function,and its coactivators in myocardial injury in chronic KD.Furthermore,the usefulness of these molecules in the diagnosis of chronic KD was assessed.
基金The report was supported by grants from the Beijing Nova Program(No.Z121107002512053)the Beijing Health System High Level Health Technology Talent Cultivation Plan(No.2013-3-013)+3 种基金Beijing Outstanding Talent Training Program(No.2014000021223ZK32)the National Natural Science Foundation of China(No.81100143)the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support(No.ZYLX 201303)and the National Key Clinical Speciality Construction Project.
文摘Objective To evaluate the effects and mechanisms of glucose-insulin-potassium(GIK)on post-procedural myocardial injury(PMI)after percutaneous coronary intervention(PCI).Methods A total of 200 non-diabetic patients with documented coronary heart disease(CHD)were divided into the Group GIK and Group G,with 100 patients in each group.Patients in Group G were given intravenous infusion of glucose solution 2 hours before PCI.As compared,patients in Group GIK were given GIK.Results Both post-procedural creatine phosphokinase isoenzyme MB(CK-MB;62.1±47.8 vs.48.8±52.6 U/L,P=0.007)and cTnI(0.68±0.83 vs.0.19±0.24 ng/mL,P<0.001)in Group GIK were significantly higher than those in Group G.In Group G,9.0%and 4.0%of patients had post-procedural increases in CK-MB 1-3 times and>3 times,which were significantly lower than those in Group GIK(14.0%and 7.0%,respectively;all P values<0.01);13.0%and 7.0%of patients had post-procedural increases in cTnI 1-3 times and>3 times,which were also significantly lower than those in Group GIK(21.0%and 13.0%,respectively;all P<0.001).Pre-procedural(10.2±4.5 vs.5.1±6.3,P<0.001)and post-procedural rapid blood glucose(RBG)levels(8.9±3.9 vs.5.3±5.6,P<0.001)in Group G were higher than those in Group GIK.In adjusted logistic models,usage of GIK(compared with glucose solution)remained significantly and independently associated with higher risk of post-procedural increases in both CK-MB and cTnI levels>3 times.Furthermore,pre-procedural RBG levels<5.0mmol/L were significantly associated with higher risk of post-procedural increases in both CK-MB and cTnI levels.Conclusions In non-diabetic patients with CHD,the administration of GIK may increase the risk of PMI due to hypoglycemia induced by GIK.
文摘Severe acute respiratory syndrome coronavirus 2 infection affects not only the lungs,but also the cardiovascular system,having a major impact on patients’outcomes.Myocardial injury(MI)occurs in the context of coronavirus infectious disease 2019(COVID-19)and is associated with a higher risk of severe clinical outcome and mortality.COVID-19-related MI can have various clinical manifestations,of which the main ones are myocarditis,stress cardiomyopathy,acute coronary syndrome,and pulmonary embolism.The exact mechanisms of how MI occurs in these patients are not yet fully known.Direct injury,through direct viral myocardial invasion,and indirect injury,through interaction with angiotensin I converting enzyme 2,increased inflammation,and thrombocyte and endothelial dysfunction,could be involved in acute MI in patients with COVID-19.A better understanding of these multiple potential mechanisms may help to develop new targeted therapeutic strategies.The purpose of this review is to provide the current understanding of the potential mechanisms involved in MI induced by COVID-19 and to discuss the current progress in the therapeutic strategies.
文摘Objective This study aimed to examine the effects of microcirculatory dysfunction and 654-1intervention after cardiopulmonary resuscitation on myocardial injury.Methods Landrace pigs were divided into a sham operation group(S group,n=6),ventricular fibrillation control group(VF-C group,n=8)and 654-1 intervention group(VF-I group,n=8).Hemodynamics was recorded at baseline,at recovery of spontaneous circulation(ROSC),and 1 h,2 h,4h and 6 h thereafter.Sidestream dark field(SDF)technology was used to evaluate and monitor the microcirculation flow index,total vessel density,perfusion vessel ratio,De-Backer score,and perfusion vessel density in animal viscera at various time points.Results After administration of 654-1 at 1.5 h post-ROSC,the hemodynamics in the VF-I group,as compared with the VF-C group,was significantly improved.The visceral microcirculation detected by SDF was also significantly improved in the VF-I group.As observed through electron microscopy,significantly less myocardial tissue injury was present in the VF-I group than the VF-C group.Conclusion Administration of 654-1 inhibited excessive inflammatory by improving the state of visceral microcirculation.
基金Studio Construction Project of TCM School Heritage of National Administration of Traditional Chinese Medicine(No.LPGZS2012-14)。
文摘Objective:To observe the effect of resveratrol on the injury of diabetic cardiomyocytes and its effect on HSF1 mediated iron death.Methods:the diabetic cardiomyopathy model was established by high glucose induced H9c2,and H9c2 was exposed to normal glucose concentration as a control.Then the intervention was performed with the corresponding drugs.The cell proliferation level was detected by CCK8 method,the concentrations of LDH,SOD,MDA and iron ions were detected by kit method,and the expression levels of HSF1,apoptotic proteins(Bax and Bcl-2)and iron death marker proteins(ACSL4,GPX4 and SLC7A11)were detected by Western blot;Results:compared with the blank group,the cell activity,SOD activity,the expression of HSF1,Bcl-2,GPX4 and SLC7A11 protein in the model group decreased significantly,and the LDH activity,MDA content,Bax and ACSL4 protein expression,Bax/Bcl-2 ratio and Fe^(2+)content increased significantly(P<0.01).Compared with the model group,the activity of H9c2 cells,the activity of SOD,the expression of HSF1,Bcl-2,GPX4 and SLC7A11 protein increased significantly,and the activity of LDH,the content of MDA,the expression of Bax and ACSL4 protein,the ratio of Bax/Bcl-2 and the content of Fe^(2+)decreased significantly in the resveratrol group(P<0.01).After the intervention,the activity of H9c2 cells,the activity of SOD,the expression of HSF1,Bcl-2,GPX4 and SLC7A11 protein decreased significantly,and the activity of LDH,the content of MDA,the expression of Bax and ACSL4 protein,the ratio of Bax/Bcl-2 and the content of Fe^(2+)increased significantly in si-hsf1 group(P<0.01);Conclusion:resveratrol can inhibit cell iron death and improve high glucose induced cardiomyocyte injury by up regulating the expression of HSF1.
文摘Objectives To investigate the effect of co-exposure of myocardial ischemia and cold stress on myocardial injury in rats and the relative mechanism.Methods Myocardial ischemia model was established by ligation of left coronary artery.SD rats were randomly allocated to 4 groups; sham+normal temperature(S group),sham+cold stress(SC group),myocardial ischemia+ normal temperature(Ⅰgroup), myocardial ischemia+cold stress(IC group).On the condition of 26℃,SC and IC groups were keeped in a 4℃artificial chamber for 8h(8;00-16:00) for 4 consecu- tive days.Car diac function was assessed by echocardiography;pathological change was analyzed by HE staining;myocardial infarct size was determined by TTC staining;Bim,Caspase-3 expression in myocardium was determined by western blotting.Results It was demonstrated that co-exposure of myocardial ischemia and cold stress could significantly make the cardiac muscle in abnormal shape,increase the infarct size and the expression of Bim and Caspase-3.Conclusions Co-exposure of myocardial ischemia and cold stress may aggravate the cardiac injury,pro- apoptosis protein Bim is involved.
基金supported by grants of the National Natural Science Foundation of China to YS(82272221,32071263),ZQ(81971887,82172170)and CL(82202403)the Tianjin Natural Science Foundation to ZQ(20JCYBJC01260,20JCYBJC01230)+3 种基金the Key Laboratory of Emergency and Trauma(Hainan Medical University),Ministry of Education to YS(KLET-202018)the Fundamental Research Funds for the Central Universities,Nankai University to ZQ(63211140)the Scientific Research Project of Tianjin Education Commission to CL(2020KJ206)National College Students’Innovative Entrepreneurial Training Plan Program to RL(202210062001).
文摘Myocardial injury as one of the severe complications leads to the increasing morbidity and mortality in patients with sepsis.Recent studies reported that reactive oxygen species(ROS)-mediated ferroptosis plays a critical role in the development of heart diseases.Therefore,we hypothesized that anti-ferroptosis agent might be a novel potential therapeutic strategy for sepsis-induced cardiac injury.Herein,we demonstrated that a small biocompatible and MRI-visible melanin nanoparticles(MMPP)improves myocardial function by inhibiting ROS-related ferroptosis signaling pathway.In LPS-induced murine sepsis model,after a single dose intravenously injection of MMPP treatment,MMPP markedly alleviated the myocardial injury including cardiac function and heart structure disorder through suppressing iron-accumulation induced ferroptosis.In vitro,MMPP inhibited cardiomyocyte death by attenuating oxidative stress,inflammation and maintaining mitochondrial homeostasis.Collectively,our findings demonstrated that MMPP protected heart against sepsis-induced myocardial injury via inhibiting ferroptosis and inflammation,which might be a novel therapeutic approach in future.
基金supported by National Natural Science Foundation of China(Grant No.81860873 and 81960864)the Scientific and Technological Projects of Guizhou Province(Qian Kehe Jichu(2016)1401)High-level Talents Project of Guizhou Province(GUTCM(ZQ2018005)).
文摘Background:Liqi Huoxue dripping pill(LQHXDP),a traditional Chinese drug for coronary heart disease,has a protective effect on the heart of rats with myocardial ischemia-reperfusion injury(MIRI)in previous studies;however,its mechanism of action remains unclear.The purpose of this study was to investigate the protective mechanism of LQHXDP on MIRI in rats and its relationship with the PI3K/Akt signaling pathway.Methods:In this study,Sprague-Dawley rats were pre-infused with LQHXDP(175 mg/kg/d)for 10 days.PI3K inhibitor LY294002(0.3 mg/kg)was intravenously injected 15 minutes before ischemia.The rat model of MIRI was established by ligating the left anterior descending coronary artery.Subsequently,cardiac hemodynamics,serum myocardial injury markers,inflammatory factors,myocardial infarct size,antioxidant indexes,myocardial histopathology,and phosphorylation levels of key proteins of PI3K/Akt signaling pathway were assessed in rats.Results:LQHXDP was found to improve cardiac hemodynamic indexes,reduce serum creatine kinase MB isoenzyme activity and cardiac troponin and heart-type fatty acid binding protein levels,lower serum interleukin-1 beta,interleukin-6 and tumour necrosis factorαlevels,reduce the myocardial infarct size and enhance the antioxidant capacity of myocardial tissue in MIRI rats.Pathological analysis revealed that LQHXDP attenuated the extent of myocardial injury and protected mitochondria from damage in MIRI rats.Immunoblot analysis revealed that LQHXDP increased the expression levels of p-Akt and p-GSK-3βin MIRI rat cardiomyocytes.PI3K inhibitor LY294002 could impair these effects of LQHXDP.Conclusion:LQHXDP attenuated myocardial injury,attenuated oxidative stress injury and reduced inflammatory response in MIRI rats,and its protective effects were mediated by activating of PI3K/Akt/GSK-3βsignaling pathway.
基金grant of National Key Research and Development Program of China(2022YFC3400700)National Natural Science Foundation of China(Nos.82241034,82370397,31971358,U22A20266 and C-0052)+2 种基金Top-Notch Talent Program of Hubei Province and Tongji Hospital(No.2021YBJRC005)Hubei Provincial Key Research and Developmental Program(2022BCA037)Hubei Provincial Natural Science Foundation of China(2017CFB536).
文摘Myocardial injury is one of the most common comorbidity in SARS-CoV-2 infected patients,and has poor prognosis.However,the incidence of myocardial injury in patients with SARS-CoV-2 infection has not been sufficiently investigated during the Omicron wave.We conducted a retrospective study of 2690 patients with confirmed SARS-CoV-2 Omicron infection from Tongji Hospital.The results indicated that the myocardial injury accounted for 30.8%of the total patients with SARS-CoV-2 infection and was associated with higher in-hospital mortality than those without injury before and after propensity score matching(PSM)[adjusted hazard ratio(HR),10.61;95%confidence interval(CI),7.76–14.51;P<0.001;adjusted HR,2.70;95%CI,1.86–3.93;P<0.001;respectively].Further,the levels of cytokines(IL-1β,IL-6,IL-10,and TNF-α)in patients with myocardial injury were higher than those without injury,and the higher levels of cytokines in the myocardial injury group were associated with increased mortality.Administration of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers(ACEI/ARB)could significantly reduce the mortality in patients with myocardial injury(adjusted HR,0.52;95%CI,0.38–0.71;P<0.001).Additionally,the level of angiotensin II increased in patients with SARS-CoV-2 infection was even higher in myocardial injury group compared to those without injury.Collectively,the study summarized the clinical characteristic and outcome of SARS-CoV-2 infected patients with myocardial injury during the Omicron wave in China,and validated the protective role of ACEI/ARB in improving the survival of those with myocardial injury.
基金National Natural Science Foundation of China:a Metabolomic Study of the Effects of Moxibustion on Cardiac Function and Its Intervention in RA Model Rats Based on the TGF-β1/Smads Signaling Pathway (No.81403484)Anhui Province University Natural Science Fund Project of China:Exploring the Mechanism of Action of Moxibustion in AA Rats Based on Intestinal Flora and TLR4/NF-KB Signaling Pathway (No.KJ2019A0448)+2 种基金National Project Cultivation Fund Project Plan:Exploring the Mechanism of Action of Moxibustion in AA Rats Based on Intestinal Flora and TLR4/NF-KB Signaling Pathway (No.2019py01)Anhui Province Clinical Medical Research Center [Anhui Provincial Science and Technology Department Anhui Social Science (2020) No.41]the training Program of Outstanding talents in Colleges and Universities:2021 Domestic Visiting Training Program for Outstanding Young Key Teachers in Colleges and Universities (No.gxgnfx2021122)
文摘OBJECTIVE:To examine the effects of moxibustion on myocardial injury and myocardial metabolomics in rats with rheumatoid arthritis(RA)based on the transforming growth factor beta1(TGF-β1)/Smads signaling pathway.METHODS:One hundred rats were treated with saline[normal control(NC)group]or complete Freund’s adjuvant(CFA)by right plantar injection for the RA model group,and the latter were randomly divided into 4 groups.Tripterygium wilfordii polyglycoside tablets(雷公藤多苷片,TPT)have anti-inflammatory and are widely used in the clinical treatment of RA,therefore serving as a positive control group.Three days post injection rats were given TPT tablet(TPT group),acupuncture therapy(APT group),and moxibustion treatment(MOX group)for 15 consecutive days,while NC group and model group were equally grasped and fixed and received normal saline.Rat joint swelling scores and arthritis index(AI)were evaluated in each group before the CFA challenge,therapy and after receiving therapy.Myocardial ultrastructure was observed by electron microscope.Enzyme-linked immunosorbent assay was used to detect cardiac troponin I(cTnI)levels in rat myocardial tissue.Quantitative reverse transcription polymerase chain reaction and Western blotting analysis were used to measure the mRNA and protein levels of TGF-βsignaling molecules including TGF-β1,Smad2,Smad3,Smad4,and Smad7.Myocardial metabolomics was analyzed using gas chromatography-mass spectrometer.RESULTS:Compared with model group,RA model rats receiving TPT,acupuncture,or moxibustion therapy all showed reduced joint swelling scores and AI(all P<0.01)and improved myocardial damage,whereas rats treated with moxibustion were found to be more marked.Consistently,the expressions of cTnI,TGF-β1,Smad2,Smad3,and Smad4 were found to be elevated in model rat group in contrast to NC rats and were significantly downregulated in TPT,APT and MOX group when compared with model group,while the levels of Smad7 showed the opposite result(all P<0.01).Moreover,the dissection of metabolomics suggested a novel metabolite biomarker panel including D-Xylulose 5-phosphate,dihydroxyacetone phosphate,arachidonic acid,etc was defined and implicated in amino acid,glucose,and fatty acid metabolic processes as revealed by principal component analysis and partial least squares discriminant analysis.CONCLUSION:Moxibustion prevents RA-induced inflammatory response and offers potent therapeutic effects on myocardial dysfunctions.The protective effects might be associated with its role in TGF-β1 inactivation and metabolic reprogramming.
基金Supported by Natural Science Foundation of Sichuan Province,No.2022NSFSC0738Basic Research Funds for Central Universities,No.2682022ZTPY038Tibet Autonomous Region Science and Technology Planning Project,No.XZ2022RH001.
文摘BACKGROUND Patients with diabetes mellitus are at higher risk of myocardial ischemia/reperfusion injury(MI/RI).Shuxin decoction(SXT)is a proven recipe modification from the classic herbal formula"Wu-tou-chi-shi-zhi-wan"according to the traditional Chinese medicine theory.It has been successfully used to alleviate secondary MI/RI in patients with diabetes mellitus in the clinical setting.However,the underlying mechanism is still unclear.AIM To further determine the mechanism of SXT in attenuating MI/RI associated with diabetes.METHODS This paper presents an ensemble model combining network pharmacology and biology.The Traditional Chinese Medicine System Pharmacology Database was accessed to select key components and potential targets of the SXT.In parallel,therapeutic targets associated with MI/RI in patients with diabetes were screened from various databases including Gene Expression Omnibus,DisGeNet,Genecards,Drugbank,OMIM,and PharmGKB.The potential targets of SXT and the therapeutic targets related to MI/RI in patients with diabetes were intersected and subjected to bioinformatics analysis using the Database for Annotation,Visualization and Integrated Discovery.The major results of bioinformatics analysis were subsequently validated by animal experiments.RESULTS According to the hypothesis derived from bioinformatics analysis,SXT could possibly ameliorate lipid metabolism disorders and exert anti-apoptotic effects in MI/RI associated with diabetes by reducing oxidized low density lipoprotein(LDL)and inhibiting the advanced glycation end products(AGE)-receptor for AGE(RAGE)signaling pathway.Subsequent animal experiments confirmed the hypothesis.The treatment with a dose of SXT(2.8 g/kg/d)resulted in a reduction in oxidized LDL,AGEs,and RAGE,and regulated the level of blood lipids.Besides,the expression of apoptosis-related proteins such as Bax and cleaved caspase 3 was down-regulated,whereas Bcl-2 expression was up-regulated.The findings indicated that SXT could inhibit myocardial apoptosis and improve cardiac function in MI/RI in diabetic rats.CONCLUSION This study indicated the active components and underlying molecular therapeutic mechanisms of SXT in MI/RI with diabetes.Moreover,animal experiments verified that SXT could regulate the level of blood lipids,alleviate cardiomyocyte apoptosis,and improve cardiac function through the AGE-RAGE signaling pathway.
基金We acknowledge the teachers from the Institute of Radiation Medicine,Chinese Academy of Medical Sciences for the I/R help in animal experiments。
文摘Background:Currently,no drugs can specifically improve clinical cardiac ischemia-reperfusion injury or the prognosis of hemodialysis.Salvianolic acid B(SalB)is a widely used cardiac protectant;however,its clinical application is limited by its low oral bioavailability and poor intestinal absorption.The exploration of its preparation and clinical applications has become a research hotspot in recent years.Methods:To determine whether mesoporous silica nanoparticles(MSNs)efficiently delivered SalB to the heart and SalB@MSNs-RhB reduced myocardial ischemia-reperfusion injury,we constructed a myocardial ischemia-reperfusion male rat model,hypoxia/reoxygenation cardiomyocytes,and treated them with SalB@MSNs-RhB.Results:SalB@MSNs-RhB showed improved bioavailability,therapeutic effect,heightened JAK2/STAT3-dependent pro-survival signaling,and antioxidant responses,thereby protecting cardiomyocytes from ischemia-reperfusion injury-induced oxidative stress and apoptosis.Conclusion:This use of SalB-loaded nanoparticles and investigation of their mechanism of action may provide a new strategy for treating cardiomyocytes.Thus,hypoxia/reoxygenation promotes the clinical application of SalB.
文摘Purpose: Ischemia-reperfusion (I/R) injury exacerbates myocardial cell death (including apoptosis and necrosis), leading to complications such as arrhythmias, myocardial stenosis, microvascular obstruction and heart failure, and it is particularly important to seek new strategies to mitigate reperfusion injury. In this paper, we will investigate whether atorvastatin can alleviate myocardial ischemia-reperfusion injury and verify its molecular mechanism. Methods: We successfully constructed a hypoxia-reperfusion (H/R) H9c2 cell model and transfected miR-26a-5p mimic, miR-26a-5p inhibitor and its negative control NC-mimic or NC-inhibitor into H9c2 cells using a transfection kit. The expression of miR-26a-5p and FOXO1 were detected by RT-qPCR assay, the expression of related proteins by Western blot assay, the cell viability of H9c2 cells by CCK-8 assay, the apoptosis rate of H9c2 cells by flow cytometry, the CK and LDH activity in cells by CK and LDH assay kits. The targeting relationship between miR-26a-5p and FOXO1 was verified by dual luciferase reporter gene assay. Results: MiR-26a-5p expression was decreased in H/R-induced cells and FOXO1 expression was increased in H/R-induced cells. Atorvastatin alleviated H/R injury in cardiomyocytes and was most effective at a concentration of 1 μM. Atorvastatin alleviated H/R injury in cardiomyocytes by upregulating miR-26a-5p expression, miR-26a-5p and FOXO1 were negatively regulated by targeting. Conclusion: Atorvastatin can alleviate H/R injury in cardiomyocytes by regulating miR-26a-5p/FOXO1.