硝酸盐后处理对心肌缺血再灌注损伤过程中内质网应激的影响研究

Effect of nitrates postconditioning on the endoplasmic reticulum stress during the period of myocardial ischemia-reperfusion injury

目的探讨硝酸盐后处理（PPostC）对心肌缺血再灌注损伤（MIRI）中细胞凋亡的影响，以及特异性内质网应激（ERS）损伤相关蛋向Grp78（葡萄糖调节蛋白78）和Caspase12（半胱氨酸蛋白酶12）的蛋白表达水平的变化和意义。方法Wistar大鼠24只随机分为假手术组、I／R组（缺血再灌注组）、PPostC组（硝酸盐后处理组）三组，每组8只。分别测定各组大鼠心肌缺血和梗死面积、细胞凋亡指数及Caspasel2、Grp78蛋门表达。结果假手术组未见梗死心肌和缺血心肌，PPostC组心肌缺血区面积和梗死区面积均明显小于I／R组[（42．08±4．84）％比（53.31±3．87）％，（38．13±2．05）％比（52．19±3．44）％，P均〈O．01]。假手术组心肌细胞凋亡指数明显低于I／R组和PPostC组[（6．70±2．25）％比（26．92±1．91）％比（20．54±3．05）％，P均〈0．01]。心肌组织Grp78蛋白水平假手术组亦明显低于I／R组和PPostC组，且PPostC组高于I／R组[0．13±0．03比1．04±0．16比1．22±0．11，P均〈0．01]；心肌组织Caspasel2蛋白表达水平假手术组明显低于I／R组和PPostC组，且PPostC组低于I／R组[0．11±0．01比0．41±0．06比0．33±0．04，P均〈0．01]。结论PPostC能减轻心肌细胞凋亡，而ERS激活参与了大鼠MIRI过程，推测PPostC在大鼠MIRI过程中可能通过调节ERS途径抑制细胞凋亡，改善MIRI。

Objective To investigate the effects and mechanisms of nitrates ischemic postconditioning （PPostC） on the myocardial ischemia-reperfusion injury （MIRI） model of rat, and investigate whether the endo- plasmic reticulum stress （ERS） can influence MIRI. Methods Wistar rats were randomized into three groups（n= 8 ） ： sham operation group （sham group）, ischemia-reperfusion group （ I/R group）, nitrates ischemia postcondition- ing group（PPostC group ）. Relative markers which include Ischemic size and infarct size of myocardium, cardiomy- ocyte apoptosis, Caspasel2 and Grp78 protein expression were measured respectively in every group. Results There were no infarct and ischemic myocardium in sham group. Compared with I/R group, PPostC significantly de- creased the myocardial ischemic area, myocardial infarct size, and cardiomyocyte apoptosis （P〈0.01）. Compared with sham group, the Caspasel2 and Grp78 protein expressions in I/R and PPostC groups significantly increased （P〈0.05）. Compared with I/R group, the Caspasel2 protein expression in PPostC group significantly decreased （P〈0.01）, while Grp78 protein expression in PPostC group significantly increased （P〈0.01）. Conclusion PPostC can reduce the myocardial ischemia-reperfusion injury via decreasing the myocardial ischemic and infarct size, and cardiomyocyte apoptosis. Nitrates ischemic postconditioning can decrease cardiomyocyte apoptosis via lower the regulation ERS.