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目的观察吡格列酮对大鼠在体心肌缺血再灌注时心肌细胞凋亡的影响。方法实验动物随机分为2组,一为缺血30min再灌注30min组,进一步分为假手术组(n=5)、模型组(即溶剂对照组,n=6)和吡格列酮组(3mg/kg,n=7),测定心肌梗死面积;另一为缺血30min再灌注2h组,然后进一步分为假手术组(n=5)、模型组(n=6)及吡格列酮0·3mg/kg组(n=6)、1mg/kg组(n=7)和3mg/kg组(n=6),各用药组于缺血前30min静脉注射给药。然后,取心脏标本,石蜡包埋后切片,免疫组化检测凋亡蛋白Bax、Bcl-2、Caspase-3、PPARγ蛋白质表达,原位杂交方法检测PPARγmRNA表达。TUNEL法和DNA凝胶电泳观察心肌细胞凋亡。结果(1)与模型组比较,吡格列酮组梗死面积与缺血区面积之比减少28%(P<0·01),梗死面积与左室面积之比减少32%(P<0·01);(2)免疫组化和原位杂交结果示:吡格列酮0·3、1、3mg/kg可呈剂量依赖性减少Bax、Caspase-3,增加Bcl-2、PPARγ蛋白质以及PPARγmRNA表达;(3)TUNEL法检测吡格列酮可减少心肌细胞凋亡指数,3组作用均显著(P<0·05),但DNA凝胶电泳模型组、吡格列酮0·3、1mg/kg可见到DNA梯带,假手术组和吡格列酮3mg/kg则无DNA梯带。结论吡格列酮预处理可通过减少心肌细胞凋亡和梗死面积起到抗缺血再灌注损伤的作用。
Objective To observe the effect of pioglitazone on cardiomyocyte apoptosis during myocardial ischemia reperfusion in rats. Methods The experimental animals were randomly divided into 2 groups: one was ischemia-reperfusion 30 min and reperfusion 30 min, which was further divided into sham operation group (n = 5), model group (solvent control group, n = 6) and pioglitazone group (n = 6, n = 6) and pioglitazone 0.3 mg / kg (n = 7, n = 7) respectively. The other group was given ischemia for 30 minutes and then reperfusion for 2 hours. (n = 6), 1mg / kg group (n = 7) and 3mg / kg group (n = 6). The medication groups were given intravenously 30min before ischemia. Then, heart samples were taken and paraffin embedded sections were taken. The protein expressions of Bax, Bcl-2, Caspase-3 and PPARγ were detected by immunohistochemistry. The expression of PPARγ mRNA was detected by in situ hybridization. Cardiomyocyte apoptosis was observed by TUNEL and DNA gel electrophoresis. Results (1) Compared with model group, the ratio of infarction area to ischemic area in pioglitazone group decreased by 28% (P <0.01) and the ratio of infarction area to left ventricular area decreased by 32% (P <0.01). (2) The results of immunohistochemistry and in situ hybridization showed that pioglitazone 0.3, 1.3 mg / kg could decrease Bax, Caspase-3, increase Bcl-2, PPARγprotein and PPARγmRNA in a dose-dependent manner; (3) The detection of pioglitazone could decrease the apoptotic index of cardiomyocytes, and the effects of three groups were significant (P <0.05). However, in the DNA gel electrophoresis model group, pioglitazone 0.3 and lmg / kg showed DNA ladder, sham operation group Pioglitazone 3mg / kg DNA ladder without. Conclusion Pioglitazone pretreatment can prevent ischemia-reperfusion injury by decreasing myocardial apoptosis and infarct size.