The effects of water─soluble components isolated from Salvia miltiorrhiza on oxygen free radical prodction and lipid peroxidation were estimated. Five components(10 μmol/L)were shown to inhibit superoxide anion gen...The effects of water─soluble components isolated from Salvia miltiorrhiza on oxygen free radical prodction and lipid peroxidation were estimated. Five components(10 μmol/L)were shown to inhibit superoxide anion generation by xanthine─xanthine oxidase system. It was also demonstrated that six components( 100 μmol/L) prevented H_2O_2─induced hemolysis and MDA fonnation in mouse erythrocytes.The effects of Sal A, Sal B, Sal C and Ros A were dose dependent. In Langendorff rat heart, pretreatment with Sal A 20μmol/L significantly prevented MDA production induced by 30 min reoxygenation after 45 min anoxia.The results indicated that there were also other potent antioxidant componentts in Salvia milliorrhiza besides Dphl and Pal. The protection of Sal A against myocardial anoxiareoxygenation inury may be mainly ascribed to its oxygen free radical scavenging activity.展开更多
This study aimed to investigate the protective effects of zin-giberis and acniti praeparatae decoction on oxidative stress injury induced by my-ocardial ischemia reperfusion in rats. [Method] Myocardial ischemia-reper...This study aimed to investigate the protective effects of zin-giberis and acniti praeparatae decoction on oxidative stress injury induced by my-ocardial ischemia reperfusion in rats. [Method] Myocardial ischemia-reperfusion was performed by ligation of the left anterior descending coronary artery for 30 min, fol-lowed by reperfusion for 60 min. The effects of zingiberis and acniti praeparatae decoction on ECG ST segment, myocardial infarction percentage, malondialdehyde (MDA) content in the serum, superoxide dismutase (SOD) activity and other indica-tors were observed. [Result] Zingiberis and acniti praeparatae decoction could effec-tively inhibit ECG ST segment elevation caused by myocardial ischemia-reperfusion injuries, reduce the percentage of myocardial infarction, decline the content of MDA in the serum, and increase the activity of SOD. [Conclusion] Zingiberis and acniti praeparatae decoction exhibits protective effects on oxidative injuries caused by my-ocardial ischemia-reperfusion injuries in rats, which may be involved in reducing the formation of myocardial free radicals and enhancing antioxidant capacity of my-ocardium.展开更多
A physiological sequence called autophagy qualitatively determines cellular viability by removing protein aggregates and damaged cyto-plasmic constituents, and contributes significantly to the degree of myocardial isc...A physiological sequence called autophagy qualitatively determines cellular viability by removing protein aggregates and damaged cyto-plasmic constituents, and contributes significantly to the degree of myocardial ischemia-reperfusion (I/R) injury. This tightly orchestrated cata-bolic cellular‘housekeeping’ process provides cells with a new source of energy to adapt to stressful conditions. This process was first described as a pro-survival mechanism, but increasing evidence suggests that it can also lead to the demise of the cell. Autophagy has been implicated in the pathogenesis of multiple cardiac conditions including myocardial I/R injury. However, a debate persists as to whether autophagy acts as a protec-tive mechanism or contributes to the injurious effects of I/R injury in the heart. This controversy may stem from several factors including the va-riability in the experimental models and species, and the methodology used to assess autophagy. This review provides updated knowledge on the modulation and role of autophagy in isolated cardiac cells subjected to I/R, and the growing interest towards manipulating autophagy to increase the survival of cardiac myocytes under conditions of stress-most notably being I/R injury. Perturbation of this evolutionarily conserved intracellular cleansing autophagy mechanism, by targeted modulation through, among others, mammalian target of rapamycin (mTOR) inhibitors, adenosine monophosphate-activated protein kinase (AMPK) modulators, calcium lowering agents, resveratrol, longevinex, sirtuin activators, the proapoptotic gene Bnip3, IP3 and lysosome inhibitors, may confer resistance to heart cells against I/R induced cell death. Thus, therapeutic ma-nipulation of autophagy in the challenged myocardium may benefit post-infarction cardiac healing and remodeling.展开更多
Objective Several studies have indicated that miR-15a,miR-15b and miR-16 may be the important regulators of apoptosis.Since attenuate apoptosis could protect myocardium and reduce infarction size,the present study was...Objective Several studies have indicated that miR-15a,miR-15b and miR-16 may be the important regulators of apoptosis.Since attenuate apoptosis could protect myocardium and reduce infarction size,the present study was aimed to find out whether these miRNAs participate in regulating myocardial ischemia reperfusion (I/R) injury.Methods Apoptosis in mice hearts subjected to I/R was detected by TUNEL assay in vivo,while flow cytometry analysis followed by Annexin V/PI double stain in vitro was used to detect apoptosis in cultured cardiomyocytes which were subjected to hypoxia/reoxygenation (H/R).Taqman real-time quantitative PCR was used to confirm whether miR-15a/15b/16 were involved in the regulation of cardiac I/R and H/R.Results Compared to those of the controls,I/R or H/R induced apoptosis of cardiomyocytes was significantly iucreased both in vivo (24.4% ± 9.4% vs.2.2% ± 1.9%,P < 0.01,n =5) and in vitro (14.12% ±0.92% vs.2.22% ± 0.08%).The expression of miR-15a and miR-15b,but not miR-16,was increased in the mice I/R model,and the results were consistent in the H/R model.Conclusions Our data indicate miR-15 and miR-15b are up-regulated in response to cardiac I/R injury,therefore,down-regulation of miR- 15a/b may be a promising strategy to reduce myocardial apoptosis induced by cardiac I/R injury.展开更多
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 ...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.展开更多
In order to explore the effect of acupuncture preconditioning on rats' cell apoptosis with cardiac muscle re-perfusion damage and bcl-2mRNA genes, we used differentiating acupuncture and moxibustion preconditioning a...In order to explore the effect of acupuncture preconditioning on rats' cell apoptosis with cardiac muscle re-perfusion damage and bcl-2mRNA genes, we used differentiating acupuncture and moxibustion preconditioning among groups, then compared acupuncture and moxibustion preconditioning with ischemic preconditioning. The experimental results show that acupuncture and moxibustion preconditioning makes more bcl-2mRNA genes expressed and produces less cell apoptosis, furthermore, groups of acupuncture and moxibustion preconditioning for twice a day are more effective than those of ischemic ureconditioning.展开更多
Objective To simulate and assess the clinical effect of intracoronary infusion of bone marrow mononuclear cells or peripheral endothelial progenitor cells on myocardial reperfusion injury in mini-swine model. Methods...Objective To simulate and assess the clinical effect of intracoronary infusion of bone marrow mononuclear cells or peripheral endothelial progenitor cells on myocardial reperfusion injury in mini-swine model. Methods Twenty-three mini-swine with myocardial reperfusion injury were used as designed in the study protocol. About (3.54±0.90)×10^7 bone marrow mononuclear cells (MNC group, n=9) or (1.16± 1.07)× 10^7 endothelial progenitor cells (EPC group, n=7) was infused into the affected coronary segment of the swine. The other mini-swine were infused with phosphate buffered saline as control (n=7). Echocardio- graphy and hemodynamic studies were performed before and 4 weeks after cell infusion. Myocardium infarc- tion size was calculated. Stem cell differentiation was analyzed under a transmission electromicroscope. Results Left ventricular ejection fraction dropped by 0% in EPC group, 2% in MNC group, and 10% in the control group 4 weeks after cell infusion, respectively (P〈0.05). The systolic parameters increased in MNC and EPC groups but decreased in the control group. However, the diastolic parameters demonstrated no significant change in the three groups (P〉0.05). EPC decreased total infarction size more than MNC did (1.60±0.26 cm2 vs. 3.71±1.38 cm2, P〈0.05). Undermature endothelial cells and myocytes were found under transmission electromlcroscope. Conclusions Transplantation of either MNC or EPC may be beneficial to cardiac systolic function, but might not has obvious effect on diastolic function. Intracoronary infusion of EPC might be better than MNC in controlling infarction size. Both MNC and EPC may stimulate angiogenesis, inhibit flbrogenesis, and differentiate into myocardial cells.展开更多
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 Ch...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.展开更多
Background Electroacupuncture pretreatment plays a protective role in myocardial ischemia/reperfusion (I/R) injury and microRNAs (miRNAs) could act on various facets of cardiac function. However, the role of miRNA...Background Electroacupuncture pretreatment plays a protective role in myocardial ischemia/reperfusion (I/R) injury and microRNAs (miRNAs) could act on various facets of cardiac function. However, the role of miRNAs in the cardioprotection by electroacupuncture pre-treatment on myocardial I/R injury remains unknown. The purpose of the study was to examine whether miR-214 was involved in cardio-protection by electroacupuncture. Methods Using rat myocardial I/R model, we examined the role of electroacupuncture pretreatment in myocardial I/R injury and analyzed the changes in the expression of miR-214. In addition, I/R was simulated in vitro by performing oxy-gen-glucose deprivation (OGD) on H9c2 cell cultures, and the effect of electroacupuncture pretreatment on I/R injury as well as expressional level of miR-214 were examined in vitro. Furthermore, the miR-214 mimic was transfected into OGD-treated H9c2 cells, we analyzed the cell apoptosis, lactate dehydrogenase (LDH) and creatine kinase (CK) activities, intracellular free Ca2+concentration ([Ca2+]i) as well as the relative protein levels of sodium/calcium exchanger 1(NCX1), BCL2-like 11 (BIM), calmodulin-dependent protein kinase IIδ(CaMKIIδ) and Cyclophilin D (CypD). Results The in vivo results revealed that compared with the I/R group, the electroacupuncture pretreatment group showed significant decreased myocardial infarct size, as well as the increased indices of the cardiac function, including heart rate, mean arterial pressure, left ventricular systolic pressure and maximal rate for left ventricular pressure rising and declining (±dp/dt max). In addition, electroacupuncture pretreatment could inhibit the elevation of LDH and CK activities induced by I/R injury. The quantitative PCR (qPCR) results demonstrated electroacupuncture pretreatment could provide cardioprotection against myocardial I/R injury in rats with miR-214 up-regulation. In the meanwhile, in vitro, electroacupuncture pretreatment protected H9c2 cells from OGD-induced injury. Trans-fection of miR-214 mimic showed protective effects on OGD-induced injury to H9c2 cells by reducing apoptosis, decreasing LDH and CK activities, rescuing the OGD-induced Ca2+and down-regulating elevated protein levels of NCX1, BIM, CaMKIIδand CypD. Conclusions Our findings firstly demonstrated that electroacupuncture pretreatment promotes the expression of miR-214 in myocardial I/R injury and miR-214 contributes to the protective effect of electroacupuncture on myocardial I/R injury.展开更多
Researches in the field of the myocardial ischemia-reperfusion injury are attracting the attentions of clinicians for the treatments that protect cardiac muscle cells from being injured can not only help the patients ...Researches in the field of the myocardial ischemia-reperfusion injury are attracting the attentions of clinicians for the treatments that protect cardiac muscle cells from being injured can not only help the patients get recovery but also keep them in health. By clearing the free radicals and reducing calcium overload of myocardial cell, treatments with Danhong Injection will help myocardial cells survive from inflammatory reactions which are triggered by ischemia reperfusion so as that endothelial function will be improved and myocardial cell apoptosis will be inhibited. In all, Danhong Injection is an ideal medicine for protecting myocardial cell against ischemia reperfusion injury.展开更多
Objective To systematically evaluate the protection effect of electroacupuncture at "Neiguan"(内关 PC 6) on myocardial damage by means of evidence-based medicine.Methods Databases were retrieved by computer,while ...Objective To systematically evaluate the protection effect of electroacupuncture at "Neiguan"(内关 PC 6) on myocardial damage by means of evidence-based medicine.Methods Databases were retrieved by computer,while dissertation compilations and conference proceedings were searched manually.Data were analyzed statistically by using RevMan5.2software.Results Twelve studies were enrolled.Compared with myocardial ischemia reperfusion injury model group,① the magnitude of ECG STⅡ segment elevation can be reduced by means of electroacupuncture at PC 6(WMD=-73.95,95%CI[-109.69,-38.20]) and the difference was statistically significant(P0.0001);② the ATPase in myocardial cells can be increased by means of electroacupuncture at PC 6(SMD=2.28,95%Cl[1.50,3.07]) and the difference was statistically significant(P0.00001);③ the release of cTnT can be reduced by means of electroacupuncture at PC 6(WMD=-2.69,95%CI[-3.16,-2.22]) and the difference was statistically significant(P0.00001);④ the size of myocardial infarction can be reduced by means of electroacupuncture at PC 6(WMD=-17.99,95%Cl[-19.88,-16.09]) and the difference was statistically significant(P0.00001);⑤ the release of CK can be reduced by means of electroacupuncture at PC 6(WMD=-0.44,95%CI[-0.61,-0.27]) and the difference was statistically significant(P0.00001);⑥ the release of CK-MB can be reduced by means of electroacupuncture at PC 6(SMD=-2.85,95%CI[-4.46,-1.24]) and the difference was statistically significant(P0.001);⑦ the release of LDH can be reduced by means of electroacupuncture at PC 6(SMD=-2.97,95%CI[-4.87,-1.07]) and the difference was statistically significant(P0.01).Conclusion Based on the current experimental evidences,electroacupuncture at PC 6 has a higher protective effect on myocardium.展开更多
Objective: To investigate the protective effects of acuptmcture pretreatment on ischemic myocardium, the protective mechanism of acupuncture pretreatment on ischemic myocardium was explored by observing the cardiac m...Objective: To investigate the protective effects of acuptmcture pretreatment on ischemic myocardium, the protective mechanism of acupuncture pretreatment on ischemic myocardium was explored by observing the cardiac muscle cell apoptosis and the expression of HSP70 mRNA of ischemia-reperfusion injury rats treated with acupuncture pretreatment. Methods: Sixty-four Wistar rats were randomly divided into eight groups: control group, sham surgery group, ischemia-reperfusion group, ischemia pretreatment group, manual acupuncture pretreatment group (once a day), electroacupuncture pretreatment group (once a day), manual acupuncture pretreatment group (twice a day), and electroacupuncture pretreatment group (twice a day). The reperfusion model of rat myocardial ischemia was made. Expression of HSP70 mRNA was assayed by in situ hybridization, and cell apoptosis by TUNEL. Results: Compared with those in the control group and the sham surgery group, the apoptosis and the expression of HSP70 mRNA were increased in the ischemia-reperfusion group. Compared with those in the ischemia-reperfusion group, the cardiac muscle cell apoptosis was decreased and the HSP70 mRNA was increased in the rats treated with acupuncture pretreatment; meanwhile, acupuncture pretreatment twice a day had stronger effects than acupuncture pretreatment once a day and ischemia pretreatrnent. Conclusion: Acupuncture pretreatment can inhibit the cardiac muscle cell apoptosis, and up-regulate the expression of HSP70 mRNA in ischemia-reperfusion rats. Acupuncture pretreatment twice a day has stronger effects than pretreatment once a day.展开更多
Objective: To investigate effects of Shenfu injection on the concentrations of plasma tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), activity of Nuclear Factor kappa B (NF-κB) and heart tissue ultrast...Objective: To investigate effects of Shenfu injection on the concentrations of plasma tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), activity of Nuclear Factor kappa B (NF-κB) and heart tissue ultrastructure during myocardial ischemia/reperfusion (I/R) injury in rats and its potential mechanism.Methods: Myocardial ischemia/reperfusion (I/R) was produced by ligation and release of the left anterior descending coronary artery. Ischemia lasted for 30 min and reperfusion for 60 min. Twenty-four healthy male SD rats weighing 230-280 g were randomly divided into three groups (n=8, each): Group I (Sham-operation group); Group II (I/R group); Group III (Shenfu group), in which Shenfu injection (10 ml/kg) was intraperitoneally injected 30 min before ischemia in animals with I/R. The plasma concentrations of IL-6 and TNF-α were measured by ELISA, and the heart was harvested for determination of NF-κB levels by Ecl-western blot analysis. Electron microscopy was used to study its ultrastructure.Results: After reperfusion, NF-κB binding activity in myocardial nuclei and the plasma concentrations of IL-6 and TNF-α were significantly increased in Group II, compared with Group I (P< 0.01), and they were markedly reduced in Group III, compared with Group II (P< 0.01). In addition, electron microscopic examination showed more serious injury of the myocardium ultrastructure in Group II, while in Group III the myocardial ultrastructure was similar to normal state.Conclusions: Shenfu injection inhibits NF-κB activity in I/R myocardium and leads to down-regulation of proinflammatory cytokine expression, which might be one of the molecular mechanisms of Shenfu injection in cardioprotection.展开更多
Objective: To study the pretreatment effect of adenosine on NF κB nuclear activity in ischemia/reperfusion myocardium in rats. Methods: Eighteen healthy male S D rats were randomly divided into three groups. Group I ...Objective: To study the pretreatment effect of adenosine on NF κB nuclear activity in ischemia/reperfusion myocardium in rats. Methods: Eighteen healthy male S D rats were randomly divided into three groups. Group I was the control group. The other two groups were subjected to 30 minutes of ischemia, followed by 2 hours of reperfusion. In group III, adenosine was given 40 μg·kg -1 ·min -1 30 minutes before coronary artery occlusion. The NF κB in nuclear was extracted and measured with western blot analysis. TNF α levels in myocardium were measured with enzyme linked immunosorbent assay (ELISA) system. All the data were recorded with mean±SEM, differences at the 95% confidence level were considered significant. Results: NF κB activity in the nucleus significantly increased after ischemia/reperfusion and TNF α levels changed. Adenosine significantly inhibited NF κB activity in nucleus, and concomitantly decreased the level of TNF α in myocardium. Conclusions: Adenosine modulation of NF κB activation may be the cellular molecular mechanism of decreasing of TNF a. The cardioprotective action of adenosine may be involved in the differential modulation of NF κB activation during myocardial ischemia/reperfusion.展开更多
Tanshinone ⅡA(TSⅡA) is the major bioactive constituent of Salvia miltiorrhiza Bunge,a Chinese herbal medicine,which has protective effects on myocardial ischemia/reperfusion(MIR) injury.However,the cardioprotect...Tanshinone ⅡA(TSⅡA) is the major bioactive constituent of Salvia miltiorrhiza Bunge,a Chinese herbal medicine,which has protective effects on myocardial ischemia/reperfusion(MIR) injury.However,the cardioprotective effects of TSⅡA as well as its clinical use were limited due to its poor water solubility.The objective of this study was to evaluate whether Tanshinone ⅡA derivative(TD),a new water soluble compound synthesized by TSⅡA and N-Methyl-D-Glucamine,had protective effects on MIR injury and what the related mechanism was.The cardioprotective effects of TD were evaluated and compared with TSⅡA in a rat MIR model.The results show that pretreatment with TD significantly alleviated inflammatory infiltration and exhibited antioxidant effect in MIR injury by reducing the activity of lactate dehydrogenase(LDH) and malondialdehyde(MDA),decreasing expression of nuclear factor-κ-gene binding(NF-κB) and upregulating expression of heme oxygenase(HO-1),but having no effect on the content of total superoxide dismutase(T-SOD) and m RNA expression of superoxide dismutase(SOD-1).Thus,our study reveals that TD exerted significant protective effects on MIR injury through attenuating oxidative stress and inflammatory responses.展开更多
OBJECTIVE: To observe the impact of total flavo- noids from Ganshanbian (Herba Hyperici Attenuati) on the expression of vascular smooth muscle mem-brane L-type calcium channel alpha1 C subunit (CaL-olC) and ATP-s...OBJECTIVE: To observe the impact of total flavo- noids from Ganshanbian (Herba Hyperici Attenuati) on the expression of vascular smooth muscle mem-brane L-type calcium channel alpha1 C subunit (CaL-olC) and ATP-sensitive K+ channel (KATp)-Kir6.1 mRNA, and explore the mechanisms of the antiar- rhythmic effect of Ganshanbian (Herba Hyperici At- tenuatl~ total flavonoids. METHODS: The treatment vonoids from Ganshanbian group was fed total fla- (Herba Hyperici Attenua- ti) for 7 days by gavage with 100 mg. kg-~. d 1. The blank control group and model control group were given the same amount of normal saline for 7 do Ar- rhythmias were induced by performing a myocardi- al ischemia-reperfusion and electrocardiogram was observed. Reverse transcription-polymerase chain reaction was used to detect the expression of CaL-a 1Cand KATp-Kir6.1 mRNA in the myocardial cell mem- brane of all groups of rats. RESULTS: Total flavonoids from Ganshanbian (Her- ba Hyperici Attenuat can delay the appearance of myocardial ischemia reperfusion arrhythmias, shorten the duration of myocardial ischemia reper- fusion arrhythmias, reduce heart rate, reduce cell membrane expression of CaL-a1C mRNA and en- hance the expression of K_ATp-Kir6.1 mRNA in myocar- dial ischemia-reperfusion arrhythmic rats. CONCLUSION: Total flavonoids from Ganshanbian (Herba Hyperici Attenuat can alleviate arrhythmias by affecting the expression of L-type calcium chan- nels and ATP-sensitive K_ATP channels.展开更多
OBJECTIVE: To investigate the underlying mechanism of reduced myocardial ischemia-reperfusion (I/R) injury in rats using the traditionalTibetan medicine Sanweitanxiang powder (SWTX). METHODS: Rats were randomly divide...OBJECTIVE: To investigate the underlying mechanism of reduced myocardial ischemia-reperfusion (I/R) injury in rats using the traditionalTibetan medicine Sanweitanxiang powder (SWTX). METHODS: Rats were randomly divided into six groups (n=10) as follows: (a) propranolol dinitrate control group, given propranolol dinitrate 0.02 g/kg for 10 days before I/R, (b) SWTX with a high dose group, given SWTX 1.5 g/kg for 10 days before I/R, (c) SWTX with a medium dose group, given SWTX 1.25 g/kg for 10 days before I/R, (d) sham group (Sham), in which the rat heart was exposed by pericardiotomy but without I/R, (e) SWTX with a low dose group, given SWTX 1.0 g/kg for 10 days before I/R, and (f) I/R injury group. Rats were intragastrically pretreated with propranolol dinitrate orSWTX. After that, the operation to cause ischemia and reperfusion was conducted.The histopathologic changes of rat hearts were observed by hematoxylin and eosin staining and transmission electron microscopy. Ca2+ homeostasis protein expression was determined by western blot. RESULTS: After SWTX pretreatment, the development of ultrastructural pathological changes from IR injury was attenuated. A decrease in the expression of B-cell lymphoma 2 associated X protein, and an increase in the expression of B-cell lymphoma 2 were observed. An increased activation of extracellular signal regulated kinases were found. Compared with the sham group, the expression of sarcoplasmic reticulum calcium-ATPase, phospholamban, and calsequestrin were all up-regulated after pretreatment with SWTX. CONCLUSION: The protective mechanism of SWTX pretreatment on myocardial I/R injury might be related to its effect on maintaining the balance of calcium homeostasis in rat heart.展开更多
Objective:To observe the effect of electroacupuncture(EA)pretreatment on adenine nucleotides in the myocardial tissues of the myocardial ischemia-reperfusion injury(MIRI)rats,and to explore the mechanism of EA pretrea...Objective:To observe the effect of electroacupuncture(EA)pretreatment on adenine nucleotides in the myocardial tissues of the myocardial ischemia-reperfusion injury(MIRI)rats,and to explore the mechanism of EA pretreatment on myocardial prevention and protection in MIRI rats.Methods:Forty SPF male Sprague-Dawley(SD)rats were randomly divided into 5 groups:a blank group,a sham operation group,a model group,an EA at Neiguan(PC 6)group and an EA at Hegu(LI 4)group,with 8 rats in each group.Rats in the blank group only received binding to the rat plate,30 min/time,once a day for 7 d;on the 7th day,rats in the sham operation group were subjected to threading for 40 min at the left anterior descending coronary artery without ligation,and then the rats were allowed to stand for 60 min before collection of the specimens;on the 7th day,rats in the model group were subjected to threading at the left anterior descending coronary artery with ligation,for 40 min before the blood flow was restored,and then the rats were allowed to stand for 60 min before collection of the specimens;on the 7th day of pretreatment with EA at Neiguan(PC 6)or Hegu(LI 4)for 30 min per day(once a day for 7 d),rats in the EA at Neiguan(PC 6)group and EA at Hegu(LI 4)group were subjected to modeling and sample collection same as in the model group.The left ventricular myocardium of the lower left anterior descending coronary artery was collected from rats in all 5 groups.Hematoxylin-eosin(HE)staining and transmission electron microscope(TEM)were used to observe the changes in myocardial pathological morphology.The change in the adenine nucleotide level of myocardial tissue was measured by high performance liquid chromatography(HPLC).Results:The HE staining and ultrastructure showed that the myocardial injury was severer in the model group compared with the sham operation group.Compared with the model group,the myocardial injury in the EA at Neiguan(PC 6)and the EA at Hegu(LI 4)groups was mild or hardly any.The adenine nucleotide levels in the sham operation group and the model group were all decreased compared with the blank group(all P<0.05);compared with the sham operation group,the adenine nucleotide level of the model group was also decreased,but the difference was not statistically significant(P>0.05);compared with the model group,the adenine nucleotide level in the EA at Neiguan(PC 6)group was increased(P<0.05),and the adenine nucleotide level in the EA at Hegu(LI 4)group was significantly increased(P<0.01).The adenine nucleotide level in the EA at Hegu(LI 4)group was higher than that in the EA at Neiguan(PC 6)group,but the difference was not statistically significant(P>0.05).Compared with the EA at Neiguan(PC 6)group,the levels of adenosine triphosphate(ATP),adenosine diphosphate(ADP)and adenosine monophosphate(AMP)in the EA at Hegu(LI 4)group were significantly increased(all P<0.01).Conclusion:Both EA at Neiguan(PC 6)and Hegu(LI 4)can alleviate the pathological damage to myocardium in MIRI rats,and increase the adenine nucleotide level in myocardial tissues,and thus protect MIRI rats.EA at Hegu(LI 4)has a better protective effect than Neiguan(PC 6).展开更多
文摘The effects of water─soluble components isolated from Salvia miltiorrhiza on oxygen free radical prodction and lipid peroxidation were estimated. Five components(10 μmol/L)were shown to inhibit superoxide anion generation by xanthine─xanthine oxidase system. It was also demonstrated that six components( 100 μmol/L) prevented H_2O_2─induced hemolysis and MDA fonnation in mouse erythrocytes.The effects of Sal A, Sal B, Sal C and Ros A were dose dependent. In Langendorff rat heart, pretreatment with Sal A 20μmol/L significantly prevented MDA production induced by 30 min reoxygenation after 45 min anoxia.The results indicated that there were also other potent antioxidant componentts in Salvia milliorrhiza besides Dphl and Pal. The protection of Sal A against myocardial anoxiareoxygenation inury may be mainly ascribed to its oxygen free radical scavenging activity.
基金Supported by Scientific Research Project of Guiyang College of Traditional Chinese Medicine[(2010)02]~~
文摘This study aimed to investigate the protective effects of zin-giberis and acniti praeparatae decoction on oxidative stress injury induced by my-ocardial ischemia reperfusion in rats. [Method] Myocardial ischemia-reperfusion was performed by ligation of the left anterior descending coronary artery for 30 min, fol-lowed by reperfusion for 60 min. The effects of zingiberis and acniti praeparatae decoction on ECG ST segment, myocardial infarction percentage, malondialdehyde (MDA) content in the serum, superoxide dismutase (SOD) activity and other indica-tors were observed. [Result] Zingiberis and acniti praeparatae decoction could effec-tively inhibit ECG ST segment elevation caused by myocardial ischemia-reperfusion injuries, reduce the percentage of myocardial infarction, decline the content of MDA in the serum, and increase the activity of SOD. [Conclusion] Zingiberis and acniti praeparatae decoction exhibits protective effects on oxidative injuries caused by my-ocardial ischemia-reperfusion injuries in rats, which may be involved in reducing the formation of myocardial free radicals and enhancing antioxidant capacity of my-ocardium.
文摘A physiological sequence called autophagy qualitatively determines cellular viability by removing protein aggregates and damaged cyto-plasmic constituents, and contributes significantly to the degree of myocardial ischemia-reperfusion (I/R) injury. This tightly orchestrated cata-bolic cellular‘housekeeping’ process provides cells with a new source of energy to adapt to stressful conditions. This process was first described as a pro-survival mechanism, but increasing evidence suggests that it can also lead to the demise of the cell. Autophagy has been implicated in the pathogenesis of multiple cardiac conditions including myocardial I/R injury. However, a debate persists as to whether autophagy acts as a protec-tive mechanism or contributes to the injurious effects of I/R injury in the heart. This controversy may stem from several factors including the va-riability in the experimental models and species, and the methodology used to assess autophagy. This review provides updated knowledge on the modulation and role of autophagy in isolated cardiac cells subjected to I/R, and the growing interest towards manipulating autophagy to increase the survival of cardiac myocytes under conditions of stress-most notably being I/R injury. Perturbation of this evolutionarily conserved intracellular cleansing autophagy mechanism, by targeted modulation through, among others, mammalian target of rapamycin (mTOR) inhibitors, adenosine monophosphate-activated protein kinase (AMPK) modulators, calcium lowering agents, resveratrol, longevinex, sirtuin activators, the proapoptotic gene Bnip3, IP3 and lysosome inhibitors, may confer resistance to heart cells against I/R induced cell death. Thus, therapeutic ma-nipulation of autophagy in the challenged myocardium may benefit post-infarction cardiac healing and remodeling.
文摘Objective Several studies have indicated that miR-15a,miR-15b and miR-16 may be the important regulators of apoptosis.Since attenuate apoptosis could protect myocardium and reduce infarction size,the present study was aimed to find out whether these miRNAs participate in regulating myocardial ischemia reperfusion (I/R) injury.Methods Apoptosis in mice hearts subjected to I/R was detected by TUNEL assay in vivo,while flow cytometry analysis followed by Annexin V/PI double stain in vitro was used to detect apoptosis in cultured cardiomyocytes which were subjected to hypoxia/reoxygenation (H/R).Taqman real-time quantitative PCR was used to confirm whether miR-15a/15b/16 were involved in the regulation of cardiac I/R and H/R.Results Compared to those of the controls,I/R or H/R induced apoptosis of cardiomyocytes was significantly iucreased both in vivo (24.4% ± 9.4% vs.2.2% ± 1.9%,P < 0.01,n =5) and in vitro (14.12% ±0.92% vs.2.22% ± 0.08%).The expression of miR-15a and miR-15b,but not miR-16,was increased in the mice I/R model,and the results were consistent in the H/R model.Conclusions Our data indicate miR-15 and miR-15b are up-regulated in response to cardiac I/R injury,therefore,down-regulation of miR- 15a/b may be a promising strategy to reduce myocardial apoptosis induced by cardiac I/R injury.
文摘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.
文摘In order to explore the effect of acupuncture preconditioning on rats' cell apoptosis with cardiac muscle re-perfusion damage and bcl-2mRNA genes, we used differentiating acupuncture and moxibustion preconditioning among groups, then compared acupuncture and moxibustion preconditioning with ischemic preconditioning. The experimental results show that acupuncture and moxibustion preconditioning makes more bcl-2mRNA genes expressed and produces less cell apoptosis, furthermore, groups of acupuncture and moxibustion preconditioning for twice a day are more effective than those of ischemic ureconditioning.
文摘Objective To simulate and assess the clinical effect of intracoronary infusion of bone marrow mononuclear cells or peripheral endothelial progenitor cells on myocardial reperfusion injury in mini-swine model. Methods Twenty-three mini-swine with myocardial reperfusion injury were used as designed in the study protocol. About (3.54±0.90)×10^7 bone marrow mononuclear cells (MNC group, n=9) or (1.16± 1.07)× 10^7 endothelial progenitor cells (EPC group, n=7) was infused into the affected coronary segment of the swine. The other mini-swine were infused with phosphate buffered saline as control (n=7). Echocardio- graphy and hemodynamic studies were performed before and 4 weeks after cell infusion. Myocardium infarc- tion size was calculated. Stem cell differentiation was analyzed under a transmission electromicroscope. Results Left ventricular ejection fraction dropped by 0% in EPC group, 2% in MNC group, and 10% in the control group 4 weeks after cell infusion, respectively (P〈0.05). The systolic parameters increased in MNC and EPC groups but decreased in the control group. However, the diastolic parameters demonstrated no significant change in the three groups (P〉0.05). EPC decreased total infarction size more than MNC did (1.60±0.26 cm2 vs. 3.71±1.38 cm2, P〈0.05). Undermature endothelial cells and myocytes were found under transmission electromlcroscope. Conclusions Transplantation of either MNC or EPC may be beneficial to cardiac systolic function, but might not has obvious effect on diastolic function. Intracoronary infusion of EPC might be better than MNC in controlling infarction size. Both MNC and EPC may stimulate angiogenesis, inhibit flbrogenesis, and differentiate into myocardial cells.
基金funding support from the National Natural Science Foundation of China(No.81704065)Hunan Provincial Natural Science Foundation(No.2019JJ40225)+1 种基金the Scientific Research Project of Education Department of Hunan Province(No.19B415,No.19C1393 and No.20C1392)Hunan Provincial Scientific Research Project of Chinese Medicine(No.2020015)。
文摘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.
基金This study was supported by a grant from the Hainan Provincial Nature Science Foundation
文摘Background Electroacupuncture pretreatment plays a protective role in myocardial ischemia/reperfusion (I/R) injury and microRNAs (miRNAs) could act on various facets of cardiac function. However, the role of miRNAs in the cardioprotection by electroacupuncture pre-treatment on myocardial I/R injury remains unknown. The purpose of the study was to examine whether miR-214 was involved in cardio-protection by electroacupuncture. Methods Using rat myocardial I/R model, we examined the role of electroacupuncture pretreatment in myocardial I/R injury and analyzed the changes in the expression of miR-214. In addition, I/R was simulated in vitro by performing oxy-gen-glucose deprivation (OGD) on H9c2 cell cultures, and the effect of electroacupuncture pretreatment on I/R injury as well as expressional level of miR-214 were examined in vitro. Furthermore, the miR-214 mimic was transfected into OGD-treated H9c2 cells, we analyzed the cell apoptosis, lactate dehydrogenase (LDH) and creatine kinase (CK) activities, intracellular free Ca2+concentration ([Ca2+]i) as well as the relative protein levels of sodium/calcium exchanger 1(NCX1), BCL2-like 11 (BIM), calmodulin-dependent protein kinase IIδ(CaMKIIδ) and Cyclophilin D (CypD). Results The in vivo results revealed that compared with the I/R group, the electroacupuncture pretreatment group showed significant decreased myocardial infarct size, as well as the increased indices of the cardiac function, including heart rate, mean arterial pressure, left ventricular systolic pressure and maximal rate for left ventricular pressure rising and declining (±dp/dt max). In addition, electroacupuncture pretreatment could inhibit the elevation of LDH and CK activities induced by I/R injury. The quantitative PCR (qPCR) results demonstrated electroacupuncture pretreatment could provide cardioprotection against myocardial I/R injury in rats with miR-214 up-regulation. In the meanwhile, in vitro, electroacupuncture pretreatment protected H9c2 cells from OGD-induced injury. Trans-fection of miR-214 mimic showed protective effects on OGD-induced injury to H9c2 cells by reducing apoptosis, decreasing LDH and CK activities, rescuing the OGD-induced Ca2+and down-regulating elevated protein levels of NCX1, BIM, CaMKIIδand CypD. Conclusions Our findings firstly demonstrated that electroacupuncture pretreatment promotes the expression of miR-214 in myocardial I/R injury and miR-214 contributes to the protective effect of electroacupuncture on myocardial I/R injury.
文摘Researches in the field of the myocardial ischemia-reperfusion injury are attracting the attentions of clinicians for the treatments that protect cardiac muscle cells from being injured can not only help the patients get recovery but also keep them in health. By clearing the free radicals and reducing calcium overload of myocardial cell, treatments with Danhong Injection will help myocardial cells survive from inflammatory reactions which are triggered by ischemia reperfusion so as that endothelial function will be improved and myocardial cell apoptosis will be inhibited. In all, Danhong Injection is an ideal medicine for protecting myocardial cell against ischemia reperfusion injury.
基金Supported by Natural Science Foundation of China:81403460Hubei Provincial Education and Science"The 12th Five-Year Plan"Project:2014B095
文摘Objective To systematically evaluate the protection effect of electroacupuncture at "Neiguan"(内关 PC 6) on myocardial damage by means of evidence-based medicine.Methods Databases were retrieved by computer,while dissertation compilations and conference proceedings were searched manually.Data were analyzed statistically by using RevMan5.2software.Results Twelve studies were enrolled.Compared with myocardial ischemia reperfusion injury model group,① the magnitude of ECG STⅡ segment elevation can be reduced by means of electroacupuncture at PC 6(WMD=-73.95,95%CI[-109.69,-38.20]) and the difference was statistically significant(P0.0001);② the ATPase in myocardial cells can be increased by means of electroacupuncture at PC 6(SMD=2.28,95%Cl[1.50,3.07]) and the difference was statistically significant(P0.00001);③ the release of cTnT can be reduced by means of electroacupuncture at PC 6(WMD=-2.69,95%CI[-3.16,-2.22]) and the difference was statistically significant(P0.00001);④ the size of myocardial infarction can be reduced by means of electroacupuncture at PC 6(WMD=-17.99,95%Cl[-19.88,-16.09]) and the difference was statistically significant(P0.00001);⑤ the release of CK can be reduced by means of electroacupuncture at PC 6(WMD=-0.44,95%CI[-0.61,-0.27]) and the difference was statistically significant(P0.00001);⑥ the release of CK-MB can be reduced by means of electroacupuncture at PC 6(SMD=-2.85,95%CI[-4.46,-1.24]) and the difference was statistically significant(P0.001);⑦ the release of LDH can be reduced by means of electroacupuncture at PC 6(SMD=-2.97,95%CI[-4.87,-1.07]) and the difference was statistically significant(P0.01).Conclusion Based on the current experimental evidences,electroacupuncture at PC 6 has a higher protective effect on myocardium.
文摘Objective: To investigate the protective effects of acuptmcture pretreatment on ischemic myocardium, the protective mechanism of acupuncture pretreatment on ischemic myocardium was explored by observing the cardiac muscle cell apoptosis and the expression of HSP70 mRNA of ischemia-reperfusion injury rats treated with acupuncture pretreatment. Methods: Sixty-four Wistar rats were randomly divided into eight groups: control group, sham surgery group, ischemia-reperfusion group, ischemia pretreatment group, manual acupuncture pretreatment group (once a day), electroacupuncture pretreatment group (once a day), manual acupuncture pretreatment group (twice a day), and electroacupuncture pretreatment group (twice a day). The reperfusion model of rat myocardial ischemia was made. Expression of HSP70 mRNA was assayed by in situ hybridization, and cell apoptosis by TUNEL. Results: Compared with those in the control group and the sham surgery group, the apoptosis and the expression of HSP70 mRNA were increased in the ischemia-reperfusion group. Compared with those in the ischemia-reperfusion group, the cardiac muscle cell apoptosis was decreased and the HSP70 mRNA was increased in the rats treated with acupuncture pretreatment; meanwhile, acupuncture pretreatment twice a day had stronger effects than acupuncture pretreatment once a day and ischemia pretreatrnent. Conclusion: Acupuncture pretreatment can inhibit the cardiac muscle cell apoptosis, and up-regulate the expression of HSP70 mRNA in ischemia-reperfusion rats. Acupuncture pretreatment twice a day has stronger effects than pretreatment once a day.
文摘Objective: To investigate effects of Shenfu injection on the concentrations of plasma tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), activity of Nuclear Factor kappa B (NF-κB) and heart tissue ultrastructure during myocardial ischemia/reperfusion (I/R) injury in rats and its potential mechanism.Methods: Myocardial ischemia/reperfusion (I/R) was produced by ligation and release of the left anterior descending coronary artery. Ischemia lasted for 30 min and reperfusion for 60 min. Twenty-four healthy male SD rats weighing 230-280 g were randomly divided into three groups (n=8, each): Group I (Sham-operation group); Group II (I/R group); Group III (Shenfu group), in which Shenfu injection (10 ml/kg) was intraperitoneally injected 30 min before ischemia in animals with I/R. The plasma concentrations of IL-6 and TNF-α were measured by ELISA, and the heart was harvested for determination of NF-κB levels by Ecl-western blot analysis. Electron microscopy was used to study its ultrastructure.Results: After reperfusion, NF-κB binding activity in myocardial nuclei and the plasma concentrations of IL-6 and TNF-α were significantly increased in Group II, compared with Group I (P< 0.01), and they were markedly reduced in Group III, compared with Group II (P< 0.01). In addition, electron microscopic examination showed more serious injury of the myocardium ultrastructure in Group II, while in Group III the myocardial ultrastructure was similar to normal state.Conclusions: Shenfu injection inhibits NF-κB activity in I/R myocardium and leads to down-regulation of proinflammatory cytokine expression, which might be one of the molecular mechanisms of Shenfu injection in cardioprotection.
文摘Objective: To study the pretreatment effect of adenosine on NF κB nuclear activity in ischemia/reperfusion myocardium in rats. Methods: Eighteen healthy male S D rats were randomly divided into three groups. Group I was the control group. The other two groups were subjected to 30 minutes of ischemia, followed by 2 hours of reperfusion. In group III, adenosine was given 40 μg·kg -1 ·min -1 30 minutes before coronary artery occlusion. The NF κB in nuclear was extracted and measured with western blot analysis. TNF α levels in myocardium were measured with enzyme linked immunosorbent assay (ELISA) system. All the data were recorded with mean±SEM, differences at the 95% confidence level were considered significant. Results: NF κB activity in the nucleus significantly increased after ischemia/reperfusion and TNF α levels changed. Adenosine significantly inhibited NF κB activity in nucleus, and concomitantly decreased the level of TNF α in myocardium. Conclusions: Adenosine modulation of NF κB activation may be the cellular molecular mechanism of decreasing of TNF a. The cardioprotective action of adenosine may be involved in the differential modulation of NF κB activation during myocardial ischemia/reperfusion.
基金The National Natural Science Foundation of China(Grant No.81360054)
文摘Tanshinone ⅡA(TSⅡA) is the major bioactive constituent of Salvia miltiorrhiza Bunge,a Chinese herbal medicine,which has protective effects on myocardial ischemia/reperfusion(MIR) injury.However,the cardioprotective effects of TSⅡA as well as its clinical use were limited due to its poor water solubility.The objective of this study was to evaluate whether Tanshinone ⅡA derivative(TD),a new water soluble compound synthesized by TSⅡA and N-Methyl-D-Glucamine,had protective effects on MIR injury and what the related mechanism was.The cardioprotective effects of TD were evaluated and compared with TSⅡA in a rat MIR model.The results show that pretreatment with TD significantly alleviated inflammatory infiltration and exhibited antioxidant effect in MIR injury by reducing the activity of lactate dehydrogenase(LDH) and malondialdehyde(MDA),decreasing expression of nuclear factor-κ-gene binding(NF-κB) and upregulating expression of heme oxygenase(HO-1),but having no effect on the content of total superoxide dismutase(T-SOD) and m RNA expression of superoxide dismutase(SOD-1).Thus,our study reveals that TD exerted significant protective effects on MIR injury through attenuating oxidative stress and inflammatory responses.
基金Supported by National Natural Science Foundation of China(Proteomics research on the complexes of Ganshanbian(Herba Hyperici Attenuati)and Salvia miltiorrhiza anti-reperfusion arrhythmia based on the iTRAQ technology.No.81173185)Key Project of Natural Science Foundation of Heilongjiang Province(Proteomics research on the complexes of Ganshanbian(Herba Hyperici Attenuati)and Salvia miltiorrhiza anti-reperfusion arrhythmia based on the iTRAQ technology.No.ZD201111)+1 种基金Heilongjiang Province Graduate Students Research Key Project(Proteomics research on the complexes of Ganshanbian(Herba Hyperici Attenuati)and Salvia miltiorrhiza anti-reperfusion arrhythmia based on the iTRAQ technology.No.YJSCX2012-334HLJ)Outstanding Talents Support Program of Heilongjiang University of Chinese Medicine(Proteomics research on the complexes of Ganshanbian(Herba Hyperici Attenuati)and Salvia miltiorrhiza anti-reperfusion arrhythmia based on the iTRAQ technology,2012)
文摘OBJECTIVE: To observe the impact of total flavo- noids from Ganshanbian (Herba Hyperici Attenuati) on the expression of vascular smooth muscle mem-brane L-type calcium channel alpha1 C subunit (CaL-olC) and ATP-sensitive K+ channel (KATp)-Kir6.1 mRNA, and explore the mechanisms of the antiar- rhythmic effect of Ganshanbian (Herba Hyperici At- tenuatl~ total flavonoids. METHODS: The treatment vonoids from Ganshanbian group was fed total fla- (Herba Hyperici Attenua- ti) for 7 days by gavage with 100 mg. kg-~. d 1. The blank control group and model control group were given the same amount of normal saline for 7 do Ar- rhythmias were induced by performing a myocardi- al ischemia-reperfusion and electrocardiogram was observed. Reverse transcription-polymerase chain reaction was used to detect the expression of CaL-a 1Cand KATp-Kir6.1 mRNA in the myocardial cell mem- brane of all groups of rats. RESULTS: Total flavonoids from Ganshanbian (Her- ba Hyperici Attenuat can delay the appearance of myocardial ischemia reperfusion arrhythmias, shorten the duration of myocardial ischemia reper- fusion arrhythmias, reduce heart rate, reduce cell membrane expression of CaL-a1C mRNA and en- hance the expression of K_ATp-Kir6.1 mRNA in myocar- dial ischemia-reperfusion arrhythmic rats. CONCLUSION: Total flavonoids from Ganshanbian (Herba Hyperici Attenuat can alleviate arrhythmias by affecting the expression of L-type calcium chan- nels and ATP-sensitive K_ATP channels.
基金Supported by a Grant from the National Natural Sciences Foundation of China(No.81060368)
文摘OBJECTIVE: To investigate the underlying mechanism of reduced myocardial ischemia-reperfusion (I/R) injury in rats using the traditionalTibetan medicine Sanweitanxiang powder (SWTX). METHODS: Rats were randomly divided into six groups (n=10) as follows: (a) propranolol dinitrate control group, given propranolol dinitrate 0.02 g/kg for 10 days before I/R, (b) SWTX with a high dose group, given SWTX 1.5 g/kg for 10 days before I/R, (c) SWTX with a medium dose group, given SWTX 1.25 g/kg for 10 days before I/R, (d) sham group (Sham), in which the rat heart was exposed by pericardiotomy but without I/R, (e) SWTX with a low dose group, given SWTX 1.0 g/kg for 10 days before I/R, and (f) I/R injury group. Rats were intragastrically pretreated with propranolol dinitrate orSWTX. After that, the operation to cause ischemia and reperfusion was conducted.The histopathologic changes of rat hearts were observed by hematoxylin and eosin staining and transmission electron microscopy. Ca2+ homeostasis protein expression was determined by western blot. RESULTS: After SWTX pretreatment, the development of ultrastructural pathological changes from IR injury was attenuated. A decrease in the expression of B-cell lymphoma 2 associated X protein, and an increase in the expression of B-cell lymphoma 2 were observed. An increased activation of extracellular signal regulated kinases were found. Compared with the sham group, the expression of sarcoplasmic reticulum calcium-ATPase, phospholamban, and calsequestrin were all up-regulated after pretreatment with SWTX. CONCLUSION: The protective mechanism of SWTX pretreatment on myocardial I/R injury might be related to its effect on maintaining the balance of calcium homeostasis in rat heart.
文摘Objective:To observe the effect of electroacupuncture(EA)pretreatment on adenine nucleotides in the myocardial tissues of the myocardial ischemia-reperfusion injury(MIRI)rats,and to explore the mechanism of EA pretreatment on myocardial prevention and protection in MIRI rats.Methods:Forty SPF male Sprague-Dawley(SD)rats were randomly divided into 5 groups:a blank group,a sham operation group,a model group,an EA at Neiguan(PC 6)group and an EA at Hegu(LI 4)group,with 8 rats in each group.Rats in the blank group only received binding to the rat plate,30 min/time,once a day for 7 d;on the 7th day,rats in the sham operation group were subjected to threading for 40 min at the left anterior descending coronary artery without ligation,and then the rats were allowed to stand for 60 min before collection of the specimens;on the 7th day,rats in the model group were subjected to threading at the left anterior descending coronary artery with ligation,for 40 min before the blood flow was restored,and then the rats were allowed to stand for 60 min before collection of the specimens;on the 7th day of pretreatment with EA at Neiguan(PC 6)or Hegu(LI 4)for 30 min per day(once a day for 7 d),rats in the EA at Neiguan(PC 6)group and EA at Hegu(LI 4)group were subjected to modeling and sample collection same as in the model group.The left ventricular myocardium of the lower left anterior descending coronary artery was collected from rats in all 5 groups.Hematoxylin-eosin(HE)staining and transmission electron microscope(TEM)were used to observe the changes in myocardial pathological morphology.The change in the adenine nucleotide level of myocardial tissue was measured by high performance liquid chromatography(HPLC).Results:The HE staining and ultrastructure showed that the myocardial injury was severer in the model group compared with the sham operation group.Compared with the model group,the myocardial injury in the EA at Neiguan(PC 6)and the EA at Hegu(LI 4)groups was mild or hardly any.The adenine nucleotide levels in the sham operation group and the model group were all decreased compared with the blank group(all P<0.05);compared with the sham operation group,the adenine nucleotide level of the model group was also decreased,but the difference was not statistically significant(P>0.05);compared with the model group,the adenine nucleotide level in the EA at Neiguan(PC 6)group was increased(P<0.05),and the adenine nucleotide level in the EA at Hegu(LI 4)group was significantly increased(P<0.01).The adenine nucleotide level in the EA at Hegu(LI 4)group was higher than that in the EA at Neiguan(PC 6)group,but the difference was not statistically significant(P>0.05).Compared with the EA at Neiguan(PC 6)group,the levels of adenosine triphosphate(ATP),adenosine diphosphate(ADP)and adenosine monophosphate(AMP)in the EA at Hegu(LI 4)group were significantly increased(all P<0.01).Conclusion:Both EA at Neiguan(PC 6)and Hegu(LI 4)can alleviate the pathological damage to myocardium in MIRI rats,and increase the adenine nucleotide level in myocardial tissues,and thus protect MIRI rats.EA at Hegu(LI 4)has a better protective effect than Neiguan(PC 6).