摘要
目的比较阿替洛尔和酒石酸美托洛尔对大鼠急性心肌梗死(AMI)后心肌细胞凋亡及凋亡相关基因表达的作用。方法251只雌性SD大鼠结扎左冠状动脉建立AMI模型,术后24h存活的124只随机分为AMI对照(MI组,n=43)、阿替洛尔(A组,10mg·kg-1·d-1,n=39)和酒石酸美托洛尔(B组,20mg·kg-1·d-1,n=42)治疗组;另设假手术组(S组,n=27)。各组再按观察时点随机分为48h和4周两亚组。术后24h以直接灌胃法给药。末端脱氧核苷酸转移酶介导的dUTP切口末端标记技术(TUNEL)和DNA凝胶电泳检测心肌细胞凋亡。免疫组织化学方法和Western blot检测“凋亡抑制基因”bcl-2、“凋亡促进基因”bax和“凋亡执行因子”caspase-3基因的表达。结果与AMI对照组相比,AMI后48h,A、B两组梗死区、边缘区和非梗死区的心肌细胞凋亡指数,除B组梗死区显著降低(P<0·01)外,其他指标差异均无显著性(均P>0·05);心肌细胞中bcl-2的表达除A组的非梗死区外均增加(免疫组织化学染色),bax和caspase-3的表达均无明显降低。AMI4周时,A、B两组瘢痕区及其边缘区和非梗死区的心肌细胞凋亡指数均显著降低(P<0·05,P<0·01);bcl-2、bax和caspase-3的表达均无明显变化,仅A4周组非梗死区bax的表达明显降低。Western blot显示,与AMI对照组相比,A、B两组心肌细胞中caspase-3、bcl-2和bax的表达差异均无显著性,但bcl-2/bax的比值显著增加(P<0·05),并与假手术组相当。结论阿替洛尔和酒石酸美托洛尔均能减少AMI梗死/瘢痕区、边缘区和非梗死区的心肌细胞凋亡,作用相当,此作用主要是通过增加bcl-2的表达和bcl-2/bax的比值而实现。
Objective To compare the beneficial effects of Atenolol and Metoprolol on cardiomyocyte apoptosis and related gene expressions after acute myocardial infarction （AMI） in rats. Methods AMI model was established with the ligation of anterior descending coronary artery in 251 randomly selected female SD rats. Twenty-four hours after operation, the 124 survivors were randomly assigned to AMI control group （ MI group, n = 43）, Atenolol group （group A, 10 mg·kg^-1·d^-1, n = 39）, and Metoprolol group （group B, 20 mg·kg^-1·d^-1, n = 42 ）. Sham operation group （ group S, n = 27 ） was also established. Two subgroup （ 48 h subgroup and 4 weeks subgroup） was randomly divided in each group according to the time points. Drugs were given to each treatment group by gastric gavage 24 h after ligation. Cardiomyocyte apoptosis was detected with terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling （TUNEL） and DNA ladder. Bcl-2, box and caspase-3 genes were detected with immunohistochemistry and Western blot analysis. Results Compared with AMI control group, myocyte apoptosis rate （MAR） significantly decreased only in infarction area （ P 〈 0. 01 ） in group B. Bcl-2 expression was found to increase in myocytes of infarction, border and non-infarcted areas except for non-infarcted area of group A. Changes of the expressions of box and caspase-3 was not significant. Four weeks after AMI, MAR was found to decrease significantly in scar, border and non-infarcted areas （P 〈0. 05, P 〈0.01 ） in both group A and group B. No significant changes of bcl-2, bax and caspase-3 expressions was found except for a significant decrease of bax expression in non-infarcted area of group A. As indicated by Western blot, no significant change of the expressions of caspase-3, bcl-2 and box were found in myocytes of group A and group B compared with AMI control group; however, bcl-2/bax ratio significantly increased to the same level of sham-operated group （ P 〈 0.05 ）. Conclusion Both Ate
出处
《中国医学科学院学报》
CAS
CSCD
北大核心
2006年第4期538-543,i0005-i0006,共8页
Acta Academiae Medicinae Sinicae
