心肌缺血再灌注时内皮功能紊乱与心肌细胞凋亡的相关性研究

The relationship study between endothelial dysfunction and myocardial cell apoptosis during myocardial ischemia and reperfusion

目的:探讨心肌缺血再灌注时机体内皮功能紊乱与心肌细胞凋亡之间的相关性。方法:选取63只雄性大鼠制备心肌缺血再灌注模型,采用左冠状动脉前降支(LAD)结扎方式模拟心肌缺血,并根据大鼠的缺血再灌注时间(30 min、90 min、180 min)和是否使用卡托普利将其分成观察Ⅰb组、观察Ⅰa组、观察Ⅱb组、观察Ⅱa组、观察Ⅲb组和观察Ⅲa组,对各组大鼠的循环内皮细胞(CEC)、内皮素(ET)、一氧化氮(NO)和心肌细胞凋亡率进行测定。结果:在a组大鼠中,观察组大鼠CEC、ET水平较对照组均呈现持续上升趋势,NO水平较对照组均呈现持续下降趋势(均P<0.05);在使用卡托普利进行预防性干预后,观察Ⅱb组、观察Ⅲb组大鼠CEC水平、ET水平均分别低于观察Ⅱa组、观察Ⅲa组,NO水平均分别高于观察Ⅱa组、观察Ⅲa组(均P<0.05);a组大鼠心肌细胞凋亡率均高于对照组,从高到低依次为观察Ⅲa组[(235.71±40.25)%]>观察Ⅱa组[(197.28±43.56)%]>观察Ⅰa组[(138.55±32.87)%]>对照组[(5.81±2.02)%](均P<0.05);观察Ⅱb组[(125.67±26.51)%]、观察Ⅲb组[(124.91±33.28)%]大鼠的心肌细胞凋亡率均分别低于观察Ⅱa组、观察Ⅲa组(均P<0.05)。结论:缺血再灌注可引发机体出现内皮功能紊乱与心肌细胞凋亡率上升,此种变化程度与缺血再灌注时间之间存在密切联系,但适当应用血管紧张素转化酶抑制剂可在一定程度上对心肌细胞的损伤程度进行抑制。

Objective To investigate the correlation between endothelial dysfunction and cardiomyocyte apoptosis during myocardial ischemia-reperfusion.Methods A total of 63 male rats were selected to establish the rat model of myocardial ischemia-reperfusion by the ligation of the left anterior descending(LAD)coronary artery to simulate myocardial ischemia.Rats were divided into the control group and groupⅠb,groupⅠa,groupⅡb,groupⅡa,groupⅢb and groupⅢa.Control rats were treated only with LAD threading without ligation.In observation group,at 30,90,120 min after LAD ligation(marked asⅠ,Ⅱ,Ⅲgroup respectively),loosen the ligation to simulate ischemia-reperfusion.In the observation group,captopril sublingual injection of 0.25 mg/kg before ligation were marked as group b,and as group a with no captopril injection.The circulating endothelial cells(CEC),endothelin(ET),nitric oxide(NO)and the apoptosis rate of cardiomyocytes in each group were measured.Results The CEC and ET levels showed a continuous upward trend,and a NO level showed a continuous downward trend from groupⅠa toⅡa toⅢa as compared with the control group(P<0.05).After using preventive intervention of captopril,the CEC and ET levels were lower and NO levels were higher in groupⅡb andⅢb than in groupⅡa andⅢa,respectively(P<0.05).The apoptotic rate of cardiomyocytes was higher in groupⅠa than in the control group,and the apoptotic rate from high to low were from groupⅢa[(235.71±40.25)%]to groupⅡa[(197.28±43.56)%]to groupⅠa[(138.55±32.87)%]and to the control group[(5.81±2.02)%](P<0.05).The apoptotic rate of cardiomyocytes was lower in groupⅡb[(125.67±26.51)%]andⅢb[(124.91±33.28)%]than in groupⅡa andⅢa,respectively(P<0.05).Conclusions The ischemia-reperfusion can cause endothelial dysfunction and the apoptosis of cardiomyocytes,and there is a close relationship between the degree of this lesions and the duration of ischemia-reperfusion.While,the appropriate application of angiotensin converting enzyme inhibitor can inhibit the damage of cardiomyocytes to a some extent.