Janus激酶-信号转导子与转录激活子信号通路在硫化氢后处理离体缺血再灌注大鼠心肌中的作用

目的 探讨Janus激酶-信号转导子与转录激活子(JAK2/STAT3)信号通路在硫化氢后处理(H2S)减轻离体大鼠心脏缺血/再灌注(I/R)损伤的作用.方法 应用Langendorff离体心脏灌流装置、通过停灌30 min/复灌60 min的方法建立SD大鼠I/R模型.按照处理及再灌注成分分为持续灌注对照组,I/R组...

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 ischemic/reperfusion injury. METHODS Isolated perfused rat hearts were exposed to ischemia 30 min followed by reperfusion for 60 min to establish 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 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/dt_max) 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. And the percentage of TUNEL positive nuclei to all nuclei counted was used as apoptotic index (AI). The expression of phosphorylation of STAT3 and total STAT3 was determined with Western blotting analysis at the end of reperfusion. RESULTS No differences in baseline hemodynamics were observed among the experimental groups. After reperfusion, compared with I/R group, NaHS group significantly (P<0.05) improved functional recovery and largely decreased myocardial infarct size〔(23±4)% vs (41±5）%〕(P<0.05) and cardiocyte apoptotic index 〔(22±4)% vs (43±5)%〕(P<0.05), Meanwhile p- STAT3 expression was much higher 〔(0.0450±0.0034) vs (0.0238±0.0021)〕(P<0.05). However, AG-490 abolished the cardioprotection offered by hydrogen sulfide postconditioning and increase of p-STAT3 expression. CONCLUSION Hydrogen sulfide postconditioning effectively protects isolated ischemia and reperfusion rat hearts via activating JAK2/STAT3 signaling pathway.