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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 effects of atenolol and metoprolol tartrate on cardiomyocyte apoptosis and apoptosis-related gene expression after acute myocardial infarction (AMI) in rats. Methods A total of 251 female SD rats underwent ligation of the left coronary artery (AMI) model. 124 surviving patients were randomly divided into AMI control group (MI group, n = 43), atenolol group (A group, 10 mg · kg -1 n = 39) and metoprolol tartrate (group B, 20 mg · kg -1 · d -1, n = 42). Sham-operation group (n = 27) was also established. The groups were divided into 48h and 4 week subgroups according to the observation time. 24h after administration by gavage. Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and DNA gel electrophoresis. Immunohistochemistry and Western blot were used to detect the expression of bcl-2, bax and apoptosis-caspase-3 genes. Results Compared with AMI control group, the apoptosis index of myocardial cells in infarct area, marginal area and non-infarction area in groups A and B at 48 h after AMI was significantly lower than that in group B (P <0.01) (All P> 0.05). The expression of bcl-2 in cardiomyocytes was increased (immunohistochemical staining) except for the non-infarct area in group A, the expression of bax and caspase-3 were not significant reduce. At 4 weeks after AMI, the apoptosis index of myocardial cells in scarring area, marginal area and non-infarct area of A and B groups were significantly decreased (P <0.05, P <0.01); bcl-2, bax and caspase- 3 expression had no significant change, only A4 week group non-infarct bax expression was significantly reduced. Western blot showed that there was no significant difference in the expression of caspase-3, bcl-2 and bax between A and B groups compared with AMI group, but the ratio of bcl-2 / bax was significantly increased (P <0 · 05), and with the sham group. Conclusion Both atenolol and metoprolol tartrate can reduce the apoptosis of myocardial cells in myocardial infarction / scarring, borderline and non-infarcted areas, which is similar to that of bortezomib / bax ratio and achieve.