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Aim To investigate whether hydrogen sul-fide ( H2 S ) inhibits cardiomyocyte apoptosis induced by acute myocardial ischemia in isolated perfused rat heart. Methods The myocardial ischemia injury model was replicated with Langendorff isolated perfused rat heart, and the left anterior descending coronary ar-tery was ligated for 4 h. 40 male SD rats were divided into five groups randomly: sham group, ischemia group, and NaHS groups (5,10,20μmol·L-1). The segmental heart samples were used for HE staining. Cardiomyocyte apoptosis was detected with TUNEL as-say. The expressions of caspase-3 and Cyt-C in hearts were determined with Western blot analysis. Results Myocardial cells were found to show serious disorder and coagulated zonal necrosis under light microscope, the apoptotic rate of cardiomyocytes and the expression of caspase-3 and Cyt-C were significantly increased af-ter ischemia for 4h. Perfusion of NaHS resulted in more clear cell morphology and milder pathologic chan-ges of myocardiocytes according to the HE staining a-nalysis, and the significant decrease of expression of Cyt-C. After perfusion of 10,20 μmol·L-1 NaHS,the apoptotic rate of cardiomyocytes and the expression of caspase-3 were significantly decreased. Conclusion H2 S has certain protective effects on acute myocardial ischemic injury in isolated perfused rat heart via inhibi-ting cardiomyocyte apoptosis.
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Aims To observe the changes of endoge-nous hydrogen sulfide/cystathionine-γ-lyase (H2 S/CSE)system and to study the effects of H2 S on cardiac function,H2 S/CSE and myocardial infarct volumes in acute myocardial ischemic injury in isolated hearts of rats.Methods The myocardial ischemic injury model was established by the ligation of coronary artery.The hemodynamic parameters,such as the left ventricular developed pressure (LVDP),±dp/dtmax and coronary arterial flow(CF),were respectively recorded to evalu-ate the cardiac function.The content of H2 S and the activity of CSE in cardiac tissue were detected respec-tively at each time point after ischemia.Infarct vol-umes in isolated rat hearts were determined by dual staining with Evans-blue and TTC.Results (1 )Com-pared with those of the sham group,LVDP,±dp/dtmax and CF were significantly decreased at 30 min,1,2,3, 4 h after ischemia(P<0.01),there were no statistical-ly significant differences in the content of H2 S and the activity of CSE in cardiac tissue at 3 0 min after ische-mia.But during the periods from 1 h to 4h after ische-mia,the content of H2 S and the activity of CSE in car-diac tissue were significantly decreased,the infarct volumes were greatly increased compared with those of the sham control group (P<0.05 or P<0.01 ).(2) Compared with those of the ischemia 4h group,LVDP, ±dp/dtmax and CF were significantly increased in the NaHS low,middle and high dose groups (P<0.05 or P<0.01),the content of H2S and the activity of CSE in cardiac tissue were significantly increased in the NaHS low,middle and high dose groups(P<0.05 or P<0.01 ),and the infarct volumes were significantly decreased in NaHS middle and high dose groups(P<0.01 ).Conclusion H2S and CSE are involved in myocardial ischemic injury in isolated hearts of rats. Administration of NaHS could enhance the activity of CSE,increase the content of H2 S,and reduce infarct volumes.It could be suggested that H2 S has cardiopro-tective effects on acute myocardial ischemic injury.
ABSTRACT
AIM:To investigate whether hydrogen sulfide ( H2 S) protects the hearts against inflammatory re-sponses induced by acute myocardial ischemia in isolated rat hearts .METHODS: Rat acute myocardial ischemia injury was induced by ligation of the left anterior descending coronary artery for 4 h, and the normal perfusate was replaced with NaHS (5 μmol/L, 10μmol/L and 20 μmol/L) perfusate accordingly in NaHS groups 2 h after ischemia.The changes of cardiac function in the myocardial ischemic injury rats were observed .The mRNA expression of TNF-α, IL-1β, IL-6, IL-10 and ICAM-1 was detected by real-time PCR.The protein level of nuclear factor-κB ( NF-κB) in the myocardial tissues was detected by Western blotting .RESULTS:The cardiac function in ischemia group was lower than that in sham group (P<0.01).Compared with ischemia group, perfusion of NaHS resulted in the improvement of the cardiac function (P<0.05 or P<0.01).Compared with sham group, the mRNA expression of TNF-α, IL-1β, IL-6 and ICAM-1 in the cardiac tissues was significantly increased , and the mRNA expression of IL-10 in the cardiac tissues was significantly decreased in ischemia group (P<0.01).Compared with ischemia group , the perfusion of NaHS significantly decreased the mRNA ex-pression of TNF-α, IL-1β, IL-6 and ICAM-1 ( P<0.05 or P<0.01 ) .The perfusion of NaHS at concentrations of 10μmol/L and 20μmol/L significantly increased the mRNA expression of IL-10 (P<0.01).The protein level of NF-κB in ischemia group was markedly higher than that in sham group (P<0.01).Compared with ischemia group, the perfusion of NaHS at concentrations of 10 μmol/L and 20 μmol/L significantly decreased the expression of NF-κB ( P<0.05 or P<0.01).CONCLUSION:H2S protects the hearts against acute ischemia injury through inhibition of NF-κB activation and subsequent down-regulation of NF-κB-dependent inflammatory gene expression .