激动乙醛脱氢酶2对抗糖尿病大鼠心肌缺血/再灌注损伤的作用

Effect of ALDH2 activation against myocardial ischemia/reperfusion injury in diabetic rat

目的:探讨激动乙醛脱氢酶2(ALDH2)在糖尿病大鼠心肌损伤中的作用。方法:腹腔注射55 mg/kg链脲佐菌素复制糖尿病大鼠模型,分为糖尿病组和乙醇+糖尿病组(n=8)。8周后行离体心肌缺血/再灌注(I/R),测定心室动力学指标和复灌期间冠脉流出液中乳酸脱氢酶(LDH)含量。测定空腹血糖、糖化血红蛋白(HbA1c)水平。RT-PCR和Western blot测定左心室前壁心尖组织线粒体ALDH2 mRNA和蛋白表达。结果:与正常大鼠心肌I/R相比,糖尿病大鼠左室发展压、左心室最大上升和下降速率、左室做功进一步下降,左室舒张末压抬高,复灌期冠脉流出液中LDH释放增多,心室ALDH2 mRNA和蛋白表达降低;与糖尿病大鼠心肌I/R相比,ALDH2激动剂乙醇明显促进左室发展压、左心室最大上升和下降速率、左室做功的恢复,降低左室舒张末压,同时降低HbA1c水平和LDH的释放,ALDH2 mRNA和蛋白表达增高。结论:糖尿病大鼠心肌缺血/再灌注时,心肌ALDH2表达降低;增强ALDH2在糖尿病大鼠心肌中的表达可发挥保护作用。

Objective： To observe the role of activation of aldehyde dehydrogenase 2（ALDH2） on myocardial ischemia/reperfusion（I/R） injury in diabetic rats.Methods： Diabetic rat model was simulated by intraperitoneal injection 55 mg/kg streptozotocin（STZ） and divided into diabetes and ethanol ＋ diabetes groups（n=8）.After 8 weeks,myocardial ischemia/reperfusion model was mimicked in vitro.The ventricular dynamical parameters and lactate dehydrogenase（LDH） content in coronary flow were determined.The fasting blood glucose and glycosylated hemoglobin（HbA1c） level were determined by automatic biochemistry analyzer.The ALDH2 mRNA and protein expressions of left anterior myocardium were evaluated by RT-PCR and Western blot.Results： In contrast to I/R in normal rat,in diabetic rat,left ventricular development pressure（LVDP）,maximal rise/fall rate of left ventricular pressure（±dp/dtmax） and left ventricular work（RPP） were decreased,left ventricular end diastolic pressure（LVEDP） and LDH release were increased,and ALDH2 mRNA and protein expressions were decreased;compared with I/R in diabetic rat,ALDH2 agonist ethanol significantly promoted the recovery of LVDP,±dp/dtmax,RPP,reduced HbA1c level,LVEDP and LDH released,ALDH2 mRNA and protein expressions were increased.Conclusion： In diabetic rat,the expression of ALDH2 was decreased when heart was subjected to I/R.Enhanced mitochondrial ALDH2 expression in diabetic rat could play cardiac protective role.