当归对心肌梗塞后心肌细胞凋亡及凋亡相关基因的影响

目的:探讨当归对大鼠心肌梗塞后梗塞灶边缘区心肌细胞凋亡及凋亡相关基因表达的影响。方法: 雄性Wistar大鼠随机分为假手术组(Sham组)、心梗组(MI组)、当归干预组(MI+Angelica 组)。经结扎大鼠冠状动脉左前降支制备心肌梗塞模型,MI+Angelica组于造模24 h后,每日每只大鼠腹腔注射50%当归注射液3.5~4.0ml(含生药量1.75~2 g),MI组和 Sham组注射同等剂量的生理盐水,术后 1, 2, 3, 4 周处死动物。分别采用TUNEL染色及免疫组织化学法检测心肌细胞凋亡数、心肌细胞凋亡加速基因 Bax和凋亡抑制基因 Bcl 2 的蛋白表达水平。结果:① MI组和MI+Angelica组梗塞灶边缘区均有心肌细胞凋亡; 但MI+Angelica组心肌细胞凋亡数明显低于MI组(P< 0.01); ②与Sham组相比,MI组和MI+Angelica组Bax和Bcl 2基因的蛋白表达均明显升高,加入当归干预后,进一步增加Bcl 2基因的表达(与MI组比, P< 0.01),明显抑制Bax基因的表达(与MI组比, P< 0.01)。结论:心肌梗塞后梗塞灶边缘区有大量的心肌细胞凋亡,当归通过上调凋亡抑制基因Bcl 2和下调凋亡加速基因Bax的表达, 而抑制该区的心肌细胞凋亡, 进而减少梗塞灶边缘区心肌细胞的坏死, 有助于心肌梗塞的治疗和预防心肌梗塞后并发症的发生。

Effects of Angelica on Myocardial Apoptosis and Expression of Apoptosis-Associated Genes after Myocardial Infarction

Objective: To investigate the effects of Angelica on myocardial apoptosis and the expression of apoptosis-associated genes in the infarct border zone in rats with myocardial infarction (MI).Methods: Male Wistar rats were divided into three groups as Sham, MI and MI + Angelica group. MI was induced by ligating the left anterior descending coronary artery. After 24 hours, the MI + Angelica group were treated with Angelica daily (2 g per rat, i.p.) while the Sham and MI group were treated with placebo (saline, i.p.). Rats were sacrificed at day 7, 14, 21 and 28 after operation. Myocardial apoptosis and protein expression of Bax and Bcl-2 genes were detected by TUNEL staining and immunohistochemistry. Results: ① There were apoptotic myocytes in the infarct border zone in MI and MI+Angelica groups, and the number of apoptotic myocytes were decreased significantly in MI+Angelica group compared with that in MI group (P< 0.01). ② Positive expression of Bax and Bcl-2 genes was markedly increased in the MI group and MI+Angelica group compared with that in Sham group. Angelica significantly inhibited expression of the Bax gene (P< 0.01) and significantly upgraded Bcl-2 gene expression (P< 0.01). Conclusion: Myocyte apoptosis and expression of Bax and Bcl-2 genes are significantly increased in rat hearts with MI. Angelica injection has a beneficial effect on treatment of MI because of its downregulation of Bax gene expression and its upregulation of Bcl-2 gene expression.