【摘要】 目的:探讨二甲双胍对心肌缺血再灌注大鼠心肌凋亡的影响。方法:采用结扎冠脉前降支30 min,再灌注2 h的方法制备大鼠心肌缺血再灌注模型,随机分为正常对照（NC）组、假手术（Sham）组、缺血再灌注（IR）组、二甲双胍高（HD）、中（MD）、低（LD）3个剂量组(150,300,500 mg·kg^-1),每组10只,于建模前3 d至处死前每天灌胃给药,TUNEL法检测心肌细胞凋亡,RT-PCR法检测心肌组织中HIF-1α基因表达,Western blot法检测心肌组织中Fas、Bcl-2、Bax和caspase-3蛋白表达。结果:与IR组相比,LD组、MD组和HD组大鼠24 h和7 d时心肌细胞凋亡率均降低,差异均有统计学意义（P<0.01）;与IR组相比,LD组、MD组和HD组大鼠24 h和7 d时心肌组织中HIF-1αmRNA相对表达量均降低,差异均有统计学意义（P<0.01）;与IR组相比,LD组、MD组和HD组大鼠24 h和7 d时Fas、caspase-3和Bax蛋白相对表达量均降低,而Bcl-2蛋白相对表达量均升高,差异均有统计学意义（P<0.01）。二甲双胍各剂量组的作用均呈剂量相关性,其中MD组和HD组与LD组相比,差异有统计学意义（P<0.01）。结论:二甲双胍可减少缺血-再灌注大鼠心肌细胞凋亡发生,其机制可能与改善心肌缺血环境、抑制Fas死亡信号通路激活、增加凋亡抑制因子Bcl-2表达有关。更多还原

【Abstract】 Objective: To investigate the effects of metformin on myocardial cell apoptosis during myocardial ischemia-reperfusion（ MI/R） injury in rats. Methods: The rat model of MI/R injury was prepared by coronary artery ligation for 30 min followed by 2-hour reperfusion. Then the rats were randomly divided into 6 groups: the normal control（ NC） group,the sham group,the model（ IR）group,metformin group respectively at low（ LD）,medium（ MD） and high（ HD） dose( 150,300 and 500 mg·kg^-1) with 10 ones in each. From 3 days before the model establishment to death,the rats were with gavage administration every day. The myocardial cell apoptosis was detected by the TUNEL method. The expression of HIF-1α gene in myocardial tissues was detected by the RT-PCR method. The expressions of Fas,Bcl-2,Bax and caspase-3 proteins in myocardial tissues were tested by Western blot. Results: Compared with that in the IR group,the myocardial cell apoptosis rates in LD group,MD group and HD group all decreased,and the differences were statistically significant（ P < 0. 01）,meanwhile,the relative expression levels of HIF-1α mRNA in myocardial tissues at 24 h and on the 7 th day in LD group,MD group and HD decreased,and the differences were statistically significant（ P < 0. 01）,and the relative expression levels of Fas,Bax and caspase-3 proteins at 24 h and on the 7 th day in LD group,MD group and HD group decreased,while the relative expression levels of Bcl-2 proteins increased,and the difference were statistically significant（ P < 0. 01）. The effect of metformin in each dose group was dose-dependent,and the differences were statistically significant（ P < 0. 01） when compared MD group and HD group with LD group. Conclusion: Metformin can reduce myocardial cell apoptosis during myocardial ischemia-reperfusion injury in rats. The mechanism may be related to the improvement of myocardial ischemia environment,inhibition of Fas death signaling pathway activation and increase apoptosis inhibitor Bcl-2 expression.更多还原