内源性硫化氢参与缺血后处理减轻离体大鼠心脏缺血/再灌注损伤

目的探讨内源性硫化氢是否参与缺血后处理减轻大鼠心肌缺血/再灌注损伤。方法Sprague Dawley(SD)大鼠离体心脏Langendorff灌流,平衡20min,全心缺血30min,复氧灌注60min,在复灌即刻给与短暂停灌15s/复灌15 s循环4次造成心肌缺血后处理模型。预先给予胱硫醚-γ-裂解酶(cystanthionine-γ-lysase,CSE)抑制剂炔丙基甘氨酸(L-propargylglycine,PAG),以及给予PAG后加用外源性硫化氢供体NaHS后处理,观察它们对缺血后处理的影响。记录心率(HR)、左室发展压(LVDP)、冠脉流出量(CF);检测灌流液中乳酸脱氢酶(LDH)活性、心肌组织CSE活性、硫化氢的含量以及心肌梗死面积。结果缺血/再灌注组LVDP下降、冠脉灌流液中LDH活性明显增加、心肌梗死面积增加(vsControl组,P<0.05)。缺血后处理组LVDP升高、冠脉灌流液中LDH活性下降、心肌梗死面积缩小(vsIR组,P<0.05)。PAG加缺血后处理组心肌CSE活性及H2S生成下降、并且逆转了缺血后处理的作用,而外源性硫化氢供体NaHS后处理组H2S生成回升、LVDP升高、心肌梗死面积缩小(vsIR组,P<0.05)。结论内源性硫化氢参与大鼠心肌缺血后处理减轻缺血/再灌注损伤。

Endogenous hydrogen sulfide participating in the ischemic postconditioning against cardiac ischemia /reperfusion injury

Aim To investigate whether endogenous hydrogen sulfide participated in the ischemic postconditioning against ischemia/reperfusion injury in the isolated rat hearts.Methods Isolated SD rat hearts were subjected to ischemia by stopping perfusion for 30 min followed by reperfusion for 60 min in Langendorff perfusion system,at the onset of reperfusion,4 cycles of 15 seconds reperfusion followed by 15 seconds ischemia were given for postconditioning.Intraperitoneal injection of L-propargylglycine(PAG,the inhibitor of cystanthionine-γ-lysase) half an hour before operation or administration of exogenous hydrogen sulfide donor-NaHS for postconditioning was performed to observe the impact on ischemic postconditioning.The heart rate(HR),left ventricular developed pressure(LVDP),coronary arterial flow(CF)were recorded.The activity of lactate dehydrogenase(LDH)in the coronary effluent fluid,and the activity of CSE and the content of H2S in the isolated rat hearts were measured with colorimetry method.The infarction sizes were measured with TTC dying method.Results In ischemic/reperfusion group,LVDP decreased,the activity of LDH in the coronary effluent fluid and the size of myocardial infarction increased(vs control,P<0.05).Ischemic postconditioning could improve the recovery of cardiac function,decrease the activity of LDH,and minimize the size of myocardial infarction(vs IR,P<0.05).After PAG administration,the activity of CSE and the content of H2S in the rat heart decreased(vs control,P<0.05),and the effect of ischemic postconditioning was reversed.The postconditioning of NaHS increased the content of H2S in the rat hearts,decreased the activity of LDH and minimized the size of myocardial infarction(vs IR,P<0.05).Conclusion Endogenous hydrogen sulfide participated in the ischemic postconditioning against ischemia/reperfusion injury.