Effects of Metformin on Myocardial Cell Apoptosis during Myocardial Ischemia-reperfusion Injury in Rats / 中国药师

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 meth-od. 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 7th day in LD group,MD group and HD decreased,and the differences were statistically significant(P<0.01),and the rela-tive expression levels of Fas,Bax and caspase-3 proteins at 24 h and on the 7th 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-reperfu-sion injury in rats. The mechanism may be related to the improvement of myocardial ischemia environment,inhibition of Fas death sig-naling pathway activation and increase apoptosis inhibitor Bcl-2 expression.