白藜芦醇对糖尿病大鼠心脏缺血再灌注损伤的保护作用

Protective effect of resveratrol on myocardial ischemia/reperfusion injury in diabetic rats

目的 探讨白藜芦醇（RSV）对糖尿病大鼠心肌缺血再灌注（MI/R）损伤的保护作用及其机制。方法通过腹腔注射链脲佐菌素诱导2型糖尿病大鼠模型。2周后糖尿病大鼠随机分为假手术（Sham）组、MI/R组和白藜芦醇（RSV）组。通过结扎左冠状动脉前降支诱导MI/R损伤模型。测定各组大鼠乳酸脱氢酶（LDH）、肌酸激酶（CK）、心肌肌钙蛋白I（cTnI）、心肌梗死面积、心脏收缩和舒张功能;TUNEL法检测心肌细胞凋亡指数;Western blot检测沉默信息调节因子1（SIRT1）、p53、乙酰化p53（Acetyl-p53）、Bcl-2、Bax以及细胞浆和线粒体细胞色素C（Cyt C）和凋亡诱导因子（AIF）的表达;HE染色检测心肌损伤评分。结果 与Sham组相比,MI/R组心肌梗死面积、心肌损伤评分、心肌LDH、CK、cTnI、Acetyl-p53、Bax、细胞浆Cyt C和AIF表达以及心肌细胞凋亡指数均明显增加,而心脏收缩和舒张功能明显降低,Bcl-2和SIRT1表达以及线粒体Cyt C和AIF表达明显减少。与MI/R组相比,RSV组心肌梗死面积、心肌损伤评分、心肌LDH、CK、cTnI、Acetyl-p53、Bax、细胞浆Cyt C和AIF表达以及心肌细胞凋亡指数均明显降低,而心脏收缩和舒张功能明显改善,Bcl-2和SIRT1表达以及线粒体Cyt C和AIF表达明显增加。3组之间p53表达无差异。结论 白藜芦醇可通过抗凋亡作用减轻糖尿病大鼠MI/R损伤,其作用机制与SIRT1/p53信号通路相关。

Aim To investigate the protective effect of resveratrol （RSV） on myocardial ischemia/reperfusion （MI/R） injury in diabetic rats and its mechanism. Methods Type 2 diabetic rat model was induced by intraperitone- al injection of streptozotocin. After 2 weeks, diabetic rats were randomly divided into sham operation （sham） group, MI/ R group and resveratrol （RSV） group. MI/R injury model was induced by ligation of the left anterior descending coronary artery. Lactate dehydrogenase （ LDH）, creatine kinase （ CK）, cardiac troponin I （ cTnI）, myocardial infarction area, cardiac systolic and diastolic function were measured in each group. Myocardial cell apoptosis index was detected by TUNEL assay. Western blot was used to detect the expressions of silent information regulator of transcription I （ SIRT1）, p53, acetylated p53 （Acetyl-p53）, Bcl-2, Bax, and cytosolic and mitochondrial cytochrome C （Cyt C） and apoptosis in- ducing factor （AIF）. HE staining was used to detect myocardial injury score. Results Compared with the sham group, myocardial infarction area, myocardial injury score, the expressions of myocardial LDH, CK, cTnI, Acetyl-p53, Bax, cytosolic Cyt C and AIF, and myocardial cell apoptosis index were significantly increased, while cardiac systolic and diastolic function were significantly decreased, expressions of Bcl-2, SIRT1, mitochondrial Cyt C and AIF were significantly reduced, in the MI/R group. Compared with the MI/R group, myocardial infarction area, myocardial injury score, the expressions of myocardial LDH, CK, cTnI, Acetyl-p53, Bax, cytosolic Cyt C and AIF, and myocardial cell apoptosis index were sig- nificantly decreased, while cardiac systolic and diastolic function were significantly improved, expressions of Bcl-2, SIRT1, mitochondrial Cyt C and AIF were significantly increased, in the RSV group. There was no difference of p53 expression in the three groups. Conclusion Resveratrol can attenuate ML/R injury by anti-apoptosis in diabetic rats, and its mecha- nism is related to SIRT1/p53 signaling pathway.