Effect Of Carvedilol And Metoprolol On Ischemical Reperfusion Injury About Cardiomyocyte Apoptosis In Rats

Objective: The purpose of this topic is studying protective effect of Carvedilol and Metoprolol on cardiomyocyte apoptosis and apoptosis-related genes caspase-3,p53 in myocardial ischemia-reperfusion injury rats, and comparing the differences between the two roles. Approaching Carvedilol and Metoprolol possible mechanism in ischemia-reperfusion, the purpose is to guide them at clinical application.Methods: I/R model in vivo rats were established. Healthy male SD rats (n=32) were divided into 4 groups: sham operation group (n=8): open the chest and braid without deligation the blood vessel; ischemia-reperfusion group (I/R) (n=8): left anterior descending(LAD)occlusion for 45min and reperfusion for 3h, without any intervention; Metoprolol group (n=8): left anterior descending(LAD)occlusion for 45min and reperfusion for 3h, the group was given Metoprolol 20 mg/ kg·d for 4 weeks before reperfusion; Carvedilol group (n=8): left anterior descending(LAD)occlusion for 45min and reperfusion for 3h, the group was given Carvedilol 10 mg/ kg·d for 4 weeks before reperfusion. HE stain method was used to observe cardiomyocyte by light microscope; TUNEL method was used to observe the number of apoptosis of each group; expression of p53 and caspase-3 protein were observe by immunohistochemical technique.Result: 1. The degree of myocardial damage of Metoprolol group and Carvedilol group is much litter than I/R group, and Carvedilol group is litter than Metoprolol group. 2. Compared with the sham-operation group(0.78±0.13)%, the I/R group(41.39±2.37)% has a higher rate of cardiomyocyte apoptosis (p<0.05); Compared with the I/R group, Metoprolol group(26.75±1.16)% and Carvedilol group(20.28±1.02)% significantly reduced the rate of cardiomyocyte apoptosis(p<0.05), and Carvedilol group was lower than Metoprolol group (p<0.05). 3. The results of caspase-3,p53 immunohistochemical staining: Compared with sham-operated group rats(0.05±0.01), caspase-3 expression level in I/R group(0.23±0.02)was significantly increased (p<0.05). Compared with I/R group, caspase-3 expression level in Metoprolol group(0.20±0.02)and Carvedilol group(0.18±0.03)were significantly reduced (p<0.05), and Carvedilol group was lower than Metoprolol group (p<0.05). Compared with sham-operated group rats(0.07±0.01), p53 expression level in I/R group(0.40±0.04)was significantly increased (p<0.05). Compared with I/R group, p53 expression level in Metoprolol group(0.30±0.02)and Carvedilol group(0.26±0.03)were significantly reduced (p<0.05), and Carvedilol group was lower than Metoprolol group (p<0.05).Conclusion: Carvedilol and Metoprolol can reduce myocardial injury and protect cardiomyocytes from ischemical reperfusion injury Carvedilol and Metoprolol can decrease the expression of caspase-3 and p53 and inhibit cardiomyocytes apoptosis and protect cardiomyocytes from ischemical reperfusion injury .Carvedilol group have a better protective effect than Metoprolol group.