[Beneficial effects of carvedilol on cardiomyocyte apoptosis and bcl-2/bax expression after acute myocardial infarction an experiment with rats].

Objective To investigate the beneficial effects of carvedilol on cardiomyocyte apoptosis and related gene expression after acute myocardial infarction(AMI).Methods Eighty-three female SD rats underwent ligation of left anterior descending coronary artery,and were randomly assigned to 2 groups 24 hours later: carvedilol(n=40,10 mg·kg~(-1)·d~(-1)was administered via direct gastric gavage 24 hs after the ligation,Group C)and AMI control group(n=43,normal saline of the same volume was given by gastric gavage,Group MI).Another 27 rats were used as sham operation group(Group S,administered with normal saline too).The rats of each group were killed and their hearts were taken out 48 hours and 4 weeks after observation respectively(MI-48 h,MI-4 week,C-48 h,C-4 week,S-48 h,and S-4 week subgroups).TUNEL and DNA gel electrophoresis were used to detect the cardiomyocyte apoptosis.Immunohistochemistry and Western blotting were used to detect the expression of bcl-2 and bax.Results The apoptotic indices of the infracted/scar,border and non-infarcted areas at any time-point of Group MI were all significantly higher than those of Group S(all P0.05).Only the apoptotic indices of the infracted/scar and border areas of the C-4 week subgroup were significantly lower than those of the MI-4 week subgroup(both P0.05),and were close to those of the non-infarcted area.DNA gel electrophoresis showed that the positive rate of Group S at any time-point were both 0,the positive rate of MI-48 h subgroup and C-48 h subgroup were both significantly higher than that of Group S(both P0.05) without significant difference between these 2 groups,and the positive rates of the MI-4 week subgroup and C-4 week subgroup were both 0.Immunohistochemistry showed that the bax gene expression was slightly to significantly increased in the infarcted/scar,border,and non-infarcted areas of the MI-48 h and MI-4 week subgroups.The bcl-2 expression was significantly increased only in the infracted area of the MI-48 h subgroup.The bcl-2 expression was slightly increased in the infracted and border areas of the C-48 h subgroup and the bax expression was significantly decreased in the infracted/scar area of the C-4 week subgroup.Western blotting showed that ①the bcl-2 expression of the S-4 week subgroup was significantly higher than that of the S-48 h subgroup(P0.05),②the bcl-2 expression and bax expression of the MI-48 h subgroup were significantly higher than that of the S-48 h subgroup(P0.05~0.01),the bcl-2/bax ratio of the MI-48 h subgroup was significantly lower that that of the S-48 h subgroup,however,there were no significant differences in the bcl-2 and bax expression and bcl-2/bax ratio between the MI-4 week subgroup and S-48 h subgroup(all P0.05).and ③ There were no significant difference in the bcl-2 and bax expression between Group A and Group S(all P0.05),however,the bcl-2/bax ratios at the 2 time-points of Group C were both significantly higher than those of Group MI.Conclusion Cardiomyocyte apoptosis occurs in the infarction/scar,border and non-infarcted areas after AMI.Prolonged treatment with carvedilol reduces cardiomyocyte apoptosis in the scar and border areas and increases the expression ratio of bcl-2/bax.