Role of JAK2/STAT3 signaling pathway in hydrogen sulfide postconditioning on isolated ischemia/reperfusion rat hearts

OBJECTIVE To investigate whether JAK2/STAT3 signaling pathway participated in hydrogen sulfide postconditioning protecting isolated rat hearts against ischemia/reperfusion(I/R) injury.METHODS Isolated perfused rat hearts were exposed to ischemia 30 min followed by reperfusion for 60 min to establish a rat I/R model using Langendorff apparatus.According to the different experimental protocols,SD rats were randomly assigned to the following groups:control,I/R,NaHS 10 μmol·L-1,NaHS+AG490 10 μmol·L-1,AG490 and DMSO groups.Left ventricular hemodynamics including the heart rate(HR),left ventricular developed pressure(LVDP),left ventricular end-diastolic pressure(LVEDP),the maximum rate of increase or decrease of left ventricular pressure(±dp/dtmax)were recorded at 20 min after equilibrium,at 30 min after reperfusion and at the end of reperfusion respectively.Myocardial infarct size was determined using triphenyltetrazolium chloride(TTC) staining.Myocardial TUNEL staining was determined by in situ cell death detection kit.The ratio of TUNEL positive nuclei to all the nuclei counted was used as apoptotic index(AI).The expression of phosphorylation of STAT3(P-STAT3) and total STAT3 was determined with Western blotting analysis at the end of reperfusion.RESULTS No difference in baseline hemodynamics was observed among the experimental groups.After reperfusion,compared with I/R group,NaHS group significantly improved functional recovery and largely decreased myocardial infarct size((23±4)% vs(41±5)%)(P0.05) and cardiocyte apoptotic index((22±4)% vs(43±5)%)(P0.05).Meanwhile,P-STAT3 expression was much higher((0.0450±0.0034) vs(0.0238±0.0021))(P0.05).However,AG-490 abolished the cardioprotection offered by hydrogen sulfide postconditioning and increase in P-STAT3 expression.CONCLUSION Hydrogen sulfide postconditioning effectively protects isolated ischemia and reperfusion rat hearts via activating JAK2/STAT3 signaling pathway.