一氧化氮介导的二氮嗪预处理的心肌保护机制

Cardioprotective effects of diazoxide preconditioning mediated by nitric oxide on ischemia reperfusion injured myocardium: experiment with isolated rat hearts

目的探讨二氮嗪预处理(DPC)对心肌缺血再灌注损伤保护作用的机制。方法 W istar大鼠40只,建立离体心脏Langendorff灌注模型,随机分成四组:缺血再灌注组(I/R组,n=10):在心脏平衡灌流30 min 后,缺血30 min 再灌注K-H液1 h;二氮嗪预处理组(DPC组,n=10):在心脏平衡灌流10 min 后,给予含二氮嗪(100μmol/L)的K-H液灌注5 min ,再复灌不含二氮嗪的K-H液5 min 后,再给予含二氮嗪的K-H液灌注5 min ,再复灌不含二氮嗪的K-H液5 min ,然后缺血30min ,再灌注K-H液1 h;空白对照组(n=10):用等量盐水代替二氮嗪,过程同DPC组;二甲基亚砜组(DMSO组,n=10):用DMSO代替二氮嗪,过程同DPC组。检测各组缺血前及复灌30 min 后冠脉流出液中肌酸激酶(CK)的活性、心肌组织丙二醛(MDA)及超氧化物岐化酶(SOD)活性、心肌组织一氧化氮(NO)及环磷酸鸟苷(cGMP)表达。结果 DPC组与其他组比较,冠脉流出液CK活性较明显减少(P<0.01),MDA含量明显减少(P<0.01),SOD含量明显增加(P<0.01),I/R组与DMSO及空白对照组比较差异无统计学意义(P>0.05)。心肌组织NO、cGMP含量:DPC组较其他组明显增加(P<0.01),I/R组与DMSO及空白对照组比较差异无统计学意义(P>0.05)。结论 NO介导的NO-cGMP信号通路可能参与DPC心肌保护机制的触发过程。

OBJECTIVE To explore the mechanism of protective effects on myocardium ischemia-reperfusion（I/R） injury by diazoxide preconditioning（DPC）.METHODS Isolated beating heart models of 40 Wistar rats were set up and were divided randomly into four groups.The I/R group（n=10）： Equilibrium perfusion of 30 minutes was followed by a 60 minutes reperfusion.The DPC group（n=10） had a 10-min equilibration and two cycles of 5 min of 100 μM diazoxide perfusion followed by a 5-min diazoxide-free period before the 30 min ischemia and a 60-min reperfusion.The blank control（n=10） and the DMSO group（n=10） were perfused with the same treatment as in the DPC group,excepting that diazoxide was replaced with natriichloridum and DMSO.The activity of creatine kinase（CK） in coronary outflow,the activity of malonyldialdehyde（MDA） and superoxide dismutase（SOD） in myocardium were detected.The concentrations of myocardial nitric oxide（NO） and cyclic guanosine monophosphate（cGMP） were also assessed.RESULTS In DPC group,the content of CK and MDA were significantly less than those in other groups（P〈0.01）,and the activity of SOD was much higher than other groups（P〈0.01）.However,there were no significant changes among I/R group,DMSO group and blank group（P〉0.05）.The NO and cGMP concentrations in DPC group were much higher than other groups（P〈0.01）,but there were no significant changes among I/R group,DMSO group and blank group（P〉0.05）.CONCLUSION The NO-cGMP signaling pathway mediated by NO may be involved in triggering the process of myocardial protection mechanisms of DPC.