Liqi Huoxue dripping pill protects against myocardial ischemia-reperfusion injury via the PI3K/Akt/GSK-3β signaling pathway in rats

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.

Atorvastatin Alleviates Myocardial Ischemia-Reperfusion Injury via miR-26a-5p/FOXO1

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.

Effect of salvianolic acid B-loaded mesoporous silica nanoparticles on myocardial ischemia-reperfusion injury

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.

Betulin protects against isoproterenol-induced myocardial injury by inhibiting NF-κB signaling and attenuating cardiac inflammation and oxidative stress in rats

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.

Mechanism of action of Balanophora involucrata polyphenolic compounds in the treatment of myocardial injury based on network pharmacology and molecular docking techniques

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.

The Predictive Value of NLR, IL-6, CRP, and PCT in Mycoplasmal Pneumonia with Complicated Myocardial Injury

Objective:To evaluate the dynamic changes in neutrophil-to-lymphocyte ratio(NLR),interleukin-6(IL-6),C-reactive protein(CRP),and procalcitonin(PCT)levels in children with Mycoplasma pneumoniae pneumonia(MPP)complicated by myocardial injury and to determine their predictive value both individually and in combination.Methods:150 children diagnosed with MPP at Jiujiang Maternal and Child Health Hospital between June 2023 and June 2024 were selected.Patients were divided into the myocardial damage group(MD group,n=65)and the non-myocardial damage group(non-MD group,n=85),based on the presence of myocardial injury.Ninety hospitalized children without MPP served as the control group(Con group).Myocardial enzyme profile indicators,including lactate dehydrogenase(LDH),α-hydroxybutyrate dehydrogenase(α-HBDH),aspartate aminotransferase(AST),high-sensitivity cardiac troponin I(hs-cTnI),creatine kinase(CK),and creatine kinase-MB(CK-MB),were measured using a chemiluminescent immunoassay analyzer.Serum NLR,IL-6,CRP,and PCT levels were determined using appropriate analyzers.The correlation between these markers and myocardial enzyme indicators was analyzed using Spearman correlation analysis.Multivariate logistic regression was applied to identify risk factors for myocardial injury in MPP patients.Results:Serum levels of NLR,IL-6,CRP,and PCT in the MD and non-MD groups were significantly higher than in the Con group(P<0.05),with the MD group showing higher levels than the non-MD group(P<0.05).These markers were positively correlated with myocardial enzyme indicators.Logistic regression identified elevated NLR,IL-6,CRP,PCT,LDH,α-HBDH,AST,hs-cTnI,CK,and CK-MB as risk factors for myocardial injury in MPP patients(P<0.05).Conclusion:Elevated levels of NLR,IL-6,CRP,PCT,and myocardial enzymes are significant risk factors for myocardial injury in children with MPP,offering valuable insights for prevention and prognosis.

Improved methodology for efficient establishment of the myocardial ischemia-reperfusion model in pigs through the median thoracic incision

To investigate the feasibility and effectiveness of establishing porcine ischemia-reperfusion models by ligating the left anterior descending(LAD)coronary artery,we first randomly divided 16 male Bama pigs into a sham group and a model group.After anesthesia,we separated the arteries and veins.Subsequently,we rapidly located the LAD coronary artery at the beginning of its first diagonal branch through a mid-chest incision.Then,we loosened and released the ligation line after five minutes of pre-occlusion.Finally,we ligated the LAD coronary artery in situ two minutes later and loosened the ligature 60 min after ischemia.Compared with the sham group,electrocardiogram showed multiple continuous lead ST-segment elevations,and ultrasound cardiogram showed significantly lower ejection fraction and left ventricular fractional shortening at one hour and seven days post-operation in the model group.Twenty-four hours after the operation,cardiac troponin T and creatine kinase-MB isoenzyme levels significantly increased in the model group,compared with the sham group.Hematoxylin and eosin staining showed the presence of many inflammatory cells infiltrating the interstitium of the myocardium in the model group but not in the sham group.Masson staining revealed a significant increase in infarct size in the ischemia/reperfusion group.All eight pigs in the model group recovered with normal sinus heart rates,and the survival rate was 100%.In conclusion,the method can provide an accurate and stable large animal model for preclinical research on ischemia/reperfusion with a high success rate and homogeneity of the myocardial infarction area.

Effect of rosiglitazone on rabbit model of myocardial ischemia-reperfusion injury

To explore mechanism and protective effect of rosiglitazone on myocardial ischemia reperfusion(I/R) injury.Methods:A total of 48 male Japanese white big-ear rabbits were randomly divided into control group(A),I/R group(B),low dose of rosiglitazone group(C),high dose of rosiglitazone group(D).Plasma concentration of and also reduced the concentration of plasma serum creatine kinase(CK),CK-MB.high-sensitivity C-reactive protein(hsCRP).ultrasuperoxide dismutase(SOD),malondialdehyde(MD.A).lactic acid glutathione skin peroxidase (C-SH-PX).nitric oxide(NO)and endothelin(ET) were measured 1 h later after I/R.Twenty-four hours after I/R the hearts were harvested for pathological and ultrastructural analysis.Area of myocardial infarction were tested.Results:Plasma concentration of CK,Ck-MB.hsCRP,NO. MDA and ET were decreased in C,D group compared with group B.Plasma concentration of T-SOD and GSH-Px were increased significantly in C.D group compared with group B.Compared with group B.pathological and ullraslructural changes in C and D group were slightly.There was significant difference in myocardial infarction area between group C.D and group B(P【0.05). Myocardial infarction area and arrhythmia rate were lower in group C,D compare with group B. Rosiglitazone may protect myocardium from I/R injury by enhancing T-SOD and GSH-Px concentration,inhibit inflammatory reaction,and improve endothelial function.

Effect of shenfu injection on gastrointestinal microcirculation in rabbits after myocardial ischemia-reperfusion injury

AIM： To investigate the effect of shenfu injection on gastrointestinal microcirculation after myocardial ischemic-reperfusion （IR） injury in rabbits and probe into the mechanism. METHODS： Forty healthy flap-eared white rabbits were randomly divided into 4 groups： IR injury control group （group Ⅰ ）, shenfu injection 5 mL/kg per h group （group Ⅱ）, shenfu injection 10 mL/kg per h group （group Ⅲ） and shenfu injection 20 mL/kg per h group （group Ⅳ）. The four groups were treated with Lactated Ringer＇s solution, shenfu injection 5, 10, and 20 mL/ kg per h were infused intravenously 30 min before experiment respectively. The values of hemodynamics [mean arterial pressure （MAP）, heart rate （HR）, gastric intramucosal partial pressure of carbon dioxide （PCO2）, blood gas analysis and pH] were measured and compared with those before myocardial ischemia, 60 min after myocardial ischemia and 60, 90, and 180 rain after reperfusion. RESULTS： The MAP, HR and gastric intramucosal pH were （70.50 ± 4.50） kPa, （165 ± 14） beats per rain, 7.032 ± 0.024 in group Ⅰ 60 min after myocardial ischemia, which were significantly decreased compared with those before myocardial ischemia （88.50 ± 9.75 kPa, 217 ± 18 beats per rain, 7.112 ± 0.035, P 〈 0.05）. The MAP, HR and gastric intramucosal pH were significantly decreased in group Ⅰ 60, 90, and 180 min after reperfusion （61.50 ± 5.25 kPa, 133 ± 31 beats per rain, 6.997 ± 0.025） compared with those before reperfusion respectively （P 〈 0.05）, whereas the values were insignificantly different in groups Ⅱ, Ⅲ or Ⅳ after reperfusion, compared with those before reperfusion, and there were no significant differences between groups Ⅱ, Ⅲ, and Ⅳ after reperfusion. CONCLUSION： Pre-infusion of shenfu injection has a protective effect on gastrointestinal microcirculation after myocardial IR injury in rabbits, in a dose independent manner.

Myocardial ischemia-reperfusion injury:Possible role of melatonin

Our knowledge and understanding of the pathophysiology of coronary atherosclerosis has increased enormously over the last 20 years.Reperfusion through thrombolysis or percutaneous coronary angioplasty is the standard treatment for preventing acute myocardial infarction.Early reperfusion is an absolute prerequisite for survival of the ischemic myocardium,but reperfusion itself may lead to accelerated and additional myocardial injury beyond that generated by ischemia alone.These outcomes,in a range of reperfusion-associated pathologies,are collectively termed "reperfusion injuries".Reactive oxygen species are known to be produced in large quantities in the first few minutes of the post-ischemia reperfusion process.Similarly,scientific evidence from the last 15 years has suggested that melatonin has beneficial effects on the cardiovascular system.The presence of vascular melatoninergic receptor binding sites has been demonstrated;these receptors are functionally linked to vasoconstrictor or vasodilatory effects of melatonin.It has been shown that patients with coronary heart disease have a low melatonin production rate,especially those with higher risk of cardiac infarction and/or sudden death.Melatonin attenuates molecular and cellular damage resulting from cardiac ischemia-reperfusion in which destructive free radicals are involved.

The therapeutic effect of Jiawei Danshen Decoction on myocardial ischemia-reperfusion injury by inhibiting H_(2)S-mediated autophagy signaling pathway

Objective To investigate the protective effects of Jiawei Danshen Decoction(加味丹参饮,JWDSD)on myocardial ischemia-reperfusion injury(MIRI)via the regulation of serum Hydrogen sulfide(H2S)and cardiac Beclin1,light Chain 3 A/B(LC3 A/B),p62,and autophagy protein5(ATG5).Methods Seventy specific pathogen free(SPF)Sprague-Dawley(SD)rats were randomly assigned to seven groups(n=10 in each group),including normal control,sham operation,MIRI model(model),ischemic preconditioning,Na HS,JWDSD,and JWDSD+CSE inhibitor(JWDSD+PPG)groups,and orally administered the indicated drugs for 14 d.Two hours after the last administration,the left anterior decreased branch of the coronary artery of each rat in model,Na HS,JWDSD,and JWDSD+PPG groups was ligated for 30 min and subsequently reperfused for 90 min to establish the MIRI model,and the rats in the sham operation group were only exposed to the thorax after surgery without coronary ligation.Blood samples were collected to detect H2S levels using an enzyme-linked immunosorbent assay(ELISA).Heart tissues were harvested for histopathological and immunohistochemical examination and quantitative reverse transcription polymerase chain reaction analysis of Beclin1 and ATG5 m RNA expression and Western blot analysis of Beclin1,LC3 A/B,and p62 protein expression.Results(1)The serum H2S content in model group rats was significantly reduced(P<0.01),JWDSD significantly increased the serum H2S content of model group rats(P<0.01),and the CSE inhibitor(PPG)significantly reduced H2S levels in the JWDSD group rats(P<0.01).(2)Compared with the normal control group,the myocardial tissue necrosis and cell destruction occurred in the MIRI model group,and JWDSD could alleviate the myocardial tissue necrosis of model rats,but the ameliorative effect of JWDSD could be reversed by PPG.(3)Beclin1,LC3 A/B,and p62 expression levels in the heart tissues of the model group were significantly increased(P<0.001),whereas decreased by JWDSD(P<0.05,P<0.01,and P<0.001,respectively),and the inhibitory effects of JWDSD on Beclin1,LC3 A/B,and p62 expression were partially reversed by PPG(P<0.01,P<0.05,and P<0.01,respectively).(4)The expression levels of autophagy-related genes Beclin1 and ATG5 were significantly increased in the model group(P<0.001).JWDSD clearly downregulated the expression levels of Beclin1 and ATG5(P<0.05 and P<0.001,respectively),which were reversed by PPG(P<0.001).Conclusion Our experimental data show that JWDSD can exhibit an anti-MIRI role by increasing endogenous H2S generation,and downregulating the expression of Beclin1,LC3 A/B,p62 and ATG5,which are related to inhibiting autophagy signaling.

Experimental study of miRNA-210 modified MSCs in the treatment of myocardial ischemia-reperfusion injury in rats

Objective:To investigate the therapeutic effect of microRNA210(miRNA-210)modified mesenchymal stem cells(MSCs)on myocardial ischemia-reperfusion injury(MIRI)model rats.Methods:One SD rat was sacrificed,and the lower extremity tibia and femur were isolated.MSCs were cultured by whole bone marrow adherence method to construct miRNA-210 modified MSCs.40 SD rats were divided into the sham operation group,model group,MSCs group,and miRNA-210+MSCs group,with 10 rats in each group.The left anterior descending coronary artery was ligated to prepare a model of myocardial ischemia and reperfusion.After successful modeling,50μl of MSCs suspension was injected into the tail vein of the MSCs group,and 50μl of miRNA-210 modified MSCs suspension was injected into the tail vein of the miRNA-210+MSCs group.The sham operation group and the model group were injected with the same amount of normal saline.On the 10th day after modeling,the area of myocardial infarction,morphological changes of myocardial tissue,myocardial cell apoptosis rate,and miRNA-210 expression were compared in each group.Results:The area of myocardial infarction and the rate of myocardial cell apoptosis in the model group were significantly higher than those in the sham operation group(<0.05);The area of myocardial infarction and the rate of myocardial cell apoptosis in the MSCs group were significantly lower than those in the sham operation group(P<0.05);The area of myocardial infarction and the rate of myocardial cell apoptosis in the miRNA-210+MSCs group were significantly higher than those in the MSCs group(P<0.05);The area of myocardial infarction and the rate of myocardial cell apoptosis in the miRNA-210+MSCs group were significantly lower than those in the sham operation group(P<0.05).The expression level of miRNA-210 in the myocardial tissue of the model group was significantly higher than that in the sham operation group(P<0.05);There were no significantly different in the expression level of miRNA-210 in the myocardial tissue between the MSCs group and model group(P>0.05);The expression level of miRNA-210 in the myocardial tissue of MSCs group was significantly higher than in the MSCs group,model group and sham operation group(P<0.05).HE staining showed that the miRNA-210+MSCs group had normal morphology of myocardial tissues,more uniform cytoplasmic staining,and arranged neatly myocardial fibers.The inflammatory cell infiltration and interstitial edema of the miRNA-210+MSCs group were significantly improved compared with the model group and MSCs group.Conclusion:MiRNA-210 modified MSCs can inhibit myocardial cell apoptosis in myocardial ischemia-reperfusion injury model rats,reduce the area of myocardial infarction,and improve pathological damage of myocardial tissue in rats,which has a certain therapeutic effect on myocardial ischemia-reperfusion injury.

Research progress of TRP channel's protective effect on myocardial ischemia-reperfusion injury

Transient receptor potential(TRP)channels are a type of cation channel located on the cell membrane.TRP channels are divided into 7 subfamilies(TRPC,TRPA,TRPM,TRPV,TRPN,TRPP and TRPML)and widely expressed in myocardial tissue.In recent years,with the application of gene knockout and transgenic model animals,it has been found that members of the TRP channel subfamilies TRPM,TRPC and TRPV are closely related to myocardial ischemia-reperfusion injury.The activation or inhibition of TRP channels participates in the regulation of myocardial ischemia-reperfusion injury,reduces the infarct area of the myocardium,and exerts a protective effect.Therefore,this paper first summarizes the structural characteristics of TRPM,TRPC,and TRPV and their distribution in the cardiovascular system,and then summarizes the mechanisms of TRPM,TRPC,and TRPV that regulate myocardial ischemia and reperfusion,which will provide a certain theoretical basis for treatment of myocardial ischemia-reperfusion injury.

Large animal models of cardiac ischemia-reperfusion injury:Where are we now?

Large animal models of cardiac ischemia-reperfusion are critical for evaluation of the efficacy of cardioprotective interventions prior to clinical translation.Nonetheless,current cardioprotective strategies/interventions formulated in preclinical cardiovascular research are often limited to small animal models,which are not transferable or reproducible in large animal models due to different factors such as:(i)complex and varied features of human ischemic cardiac disease(ICD),which are challenging to mimic in animal models,(ii)significant differences in surgical techniques applied,and(iii)differences in cardiovascular anatomy and physiology between small versus large animals.This article highlights the advantages and disadvantages of different large animal models of preclinical cardiac ischemic reperfusion injury(IRI),as well as the different methods used to induce and assess IRI,and the obstacles faced in using large animals for translational research in the settings of cardiac IR.

Low Selenium and Low Protein Exacerbate Myocardial Damage in Keshan Disease by Affecting the PINK1/Parkin-mediated Mitochondrial Autophagy Pathway

Objective Keshan disease(KD)is a myocardial mitochondrial disease closely related to insufficient selenium(Se)and protein intake.PTEN induced putative kinase 1(PINK1)/Parkin mediated mitochondrial autophagy regulates various physiological and pathological processes in the body.This study aimed to elucidate the relationship between PINK1/Parkin-regulated mitochondrial autophagy and KD-related myocardial injury.Methods A low Se and low protein animal model was established.One hundred Wistar rats were randomly divided into 5 groups(control group,low Se group,low protein group,low Se+low protein group,and corn from KD area group).The JC-1 method was used to detect the mitochondrial membrane potential(MMP).ELISA was used to detect serum creatine kinase MB(CK-MB),cardiac troponin I(cTnI),and mitochondrial-glutamicoxalacetic transaminase(M-GOT)levels.RT-PCR and Western blot analysis were used to detect the expression of PINK1,Parkin,sequestome 1(P62),and microtubule-associated proteins1A/1B light chain 3B(MAP1LC3B).Results The MMP was significantly decreased and the activity of CK-MB,cTnI,and M-GOT significantly increased in each experimental group(low Se group,low protein group,low Se+low protein group and corn from KD area group)compared with the control group(P<0.05 for all).The mRNA and protein expression levels of PINK1,Parkin and MAP1LC3B were profoundly increased,and those of P62 markedly decreased in the experimental groups compared with the control group(P<0.05 for all).Conclusion Low Se and low protein levels exacerbate myocardial damage in KD by affecting the PINK1/Parkin-mediated mitochondrial autophagy pathway.

The influence of pressure injury risk on the association between left ventricular ejection fraction and all-cause mortality in patients with acute myocardial infarction 80 years or older

BACKGROUND: We aimed to investigate whether the pressure injury risk mediates the association of left ventricular ejection fraction(LVEF) with all-cause death in patients with acute myocardial infarction(AMI) aged 80 years or older.METHODS: This retrospective cohort study included 677 patients with AMI aged 80 years or older from a tertiary-level hospital. Pressure injury risk was assessed using the Braden scale at admission, and three risk groups(low/minimal, intermediate, high) were defined according to the overall score of six different variables. LVEF was measured during the index hospitalization for AMI. All-cause death after hospital discharge was the primary outcome.RESULTS: Over a median follow-up period of 1,176 d(interquartile range [IQR], 722–1,900 d), 226(33.4%) patients died. Multivariate Cox regression analysis showed that reduced LVEF was associated with an increased risk of all-cause death only in the high-risk group of pressure injury(adjusted hazard ratios [HR]=1.81, 95% confidence interval [CI]: 1.03–3.20;P=0.040), but not in the low/minimal-(adjusted HR=1.29, 95%CI: 0.80–2.11;P=0.299) or intermediate-risk groups(adjusted HR=1.14, 95%CI: 0.65–2.02;P=0.651). Significant interactions were detected between pressure injury risk and LVEF(adjusted P=0.003). The cubic spline with hazard ratio plot revealed a distinct shaped curve relation between LVEF and all-cause death among different pressure injury risk groups.CONCLUSIONS: In older patients with AMI, the risk of pressure injury mediated the association between LVEF and all-cause death. The classification of older patients for both therapy and prognosis assessment appears to be improved by the incorporation of pressure injury risk assessment into AMI care management.

Research Progress on Myocardial Protection Strategies

Myocaridial protection aims to salvage myocardium from ischemia and reperfusion injury and to reduce infarct size and its consequences.After more than 30 years of development,the concept of ischemic preconditioning has evolved into"ischemic conditioning",a term that encompasses a number of related endogenous cardioprotective strategies,which can be applied either directly to the heart(ischemic preconditioning or postconditioning)or from afar,for example to a limb(remote ischemic preconditioning,preconditioning,or postconditioning).A variety of cardioprotective therapies have shown promising results in reducing infarct size and improving clinical outcomes in patients with ischemic heart disease.

L-carvone attenuates myocardial injury and dyslipidemia in rats with isoproterenol-induced cardiac hypertrophy

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.

Network-pharmacology-based research on protective effects and underlying mechanism of Shuxin decoction against myocardial ischemia/reperfusion injury with diabetes

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.

Effects of Ethyl Pyruvate on Myocardial Apoptosis and Expression of Bcl-2 and Bax Proteins after Ischemia-reperfusion in Rats

In order to study the effects of ethyl pyruvate on cardiomyocyte apoptosis following ischemia/reperfusion （I/R） in vitro and the expression of Bcl-2 and Bax proteins, isolated rat hearts were perfused in a Langendorff model. Twenty-four rats were randomly divided into 3 groups （n=8 in each group）： control group was perfused for 120 min. In the I/R group, after 30 min stabilization the injury was induced by 30 min global ischemia followed by 60 min reperfusion. Ethyl pyruvate （EP） group was set up with the same protocol as I/R group except that it was supplied with 2 mmol/L EP 15 rain before ischemia and throughout reperfusion. Myocardial malonaldehyde （MDA） content was measured. Myocardial apoptotic index （AI） was tested by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling （TUNEL） method. The expression of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax in cardiac myocytes was detected by immunohistochemistry. As compared with control group, the content of MDA, myocardial AI and the expression of Bcl-2, Bax proteins were increased significantly in I/R group, but the content of MDA, myocardial AI and the expression of Bax protein were decreased obviously and the expression of Bcl-2 protein was up-regulated in EP group （P〈0.05）. These results demonstrate that EP could inhibit apoptosis of cardiac myocytes possibly via alleviating oxidative stress, up-regulating Bcl-2 and down-regulating Bax proteins.