乙醛脱氢酶2在糖尿病大鼠心肌缺血/再灌注损伤中的抗凋亡作用

目的观察乙醛脱氢酶2(ALDH2)在糖尿病大鼠心肌缺血/再灌注凋亡发生中的作用。方法大鼠分为正常组、糖尿病组和ALDH2激动剂乙醇+糖尿病组。4周后行离体心肌缺血/再灌注(I/R)。测定复灌期间冠脉流出液中乳酸脱氢酶(LDH)含量。检测心肌组织细胞ALDH2、caspase-3的活性;RT-PCR测定左心室前壁心尖组织Bcl-2、Bax mRNA的表达。结果与正常大鼠I/R相比,糖尿病大鼠复灌期冠脉流出液中LDH释放增加,心肌组织caspase-3活性增加,ALDH2活性降低,Bcl-2/Bax mRNA比值降低;与糖尿病大鼠心肌I/R相比,ALDH2激动剂乙醇使得心肌复灌期间冠脉流出液中LDH释放减少,心肌caspase-3活性降低,ALDH2活性增高,Bcl-2/Bax mRNA比值增高。结论增强ALDH2在糖尿病大鼠心肌中的表达对缺血/再灌注损伤有明显的保护作用;其机制可能与抑制细胞凋亡的发生有关。

Anti-apoptotic role of mitochondrial aldehyde dehydrogenase 2 in myocardial ischemia/reperfusion injury in diabetic rats

Objective To evaluate the anti-apoptotic effect of aldehyde dehydrogenase 2(ALDH2) on myocardial ischemia/reperfusion(I/R) injury in diabetic rats.Methods Normal male SD rats were divided into normal,diabetes and ethanol(the agonist of ALDH2) + diabetes groups.In the latter two groups,diabetes was induced by an intraperitoneal injection of 55 mg/kg STZ.Four weeks after the modeling,myocardial I/R was mimicked ex vivo,and lactate dehydrogenase(LDH) content in the coronary flow was determined.The activities of caspase-3 and ALDH2 were evaluated,and the expressions of Bcl-2 and Bax mRNA in the left anterior myocardium were detected using RT-PCR.Results In diabetic group,LDH release and caspase-3 activity were increased,while ALDH2 activity and Bcl-2/Bax mRNA expression were decreased as compared to those in normal control group.Compared with the diabetic group,ALDH2 agonist ethanol significantly reduced LDH release and caspase-3 activity,increased ALDH2 activity and Bcl-2/Bax mRNA expression.Conclusion In diabetic rats,enhanced ALDH2 expression can offer mycardial protection possibly in relation to suppress cell apoptosis.