心肌缺血-再灌注时细胞凋亡及相关基因调控

Regulation on the Apoptosis and Related Gene Expression Induced by Myocardial Ischemia-reperfusion

关键词:  黄芪  心肌细胞  缺血-再灌注  细胞凋亡  bcl-2与bax

Key words:  Radix Astragali  Myocardial cell, Ischemia-reperfusion  Apoptosis  bcl-2 and bax

摘要:

目的:观察黄芪抑制家兔心肌缺血-再灌注时细胞凋亡的作用。方法:采用结扎冠状动脉左前降支后再通的方法,复制家兔心肌缺血再灌注的动物模型,对心肌缺血-再灌注、黄芪治疗、心肌缺血、假手术等不同情况下心肌坏死面积、心肌细胞DNA电泳、凋亡细胞的形态(TUNEL法、电镜)及bcl-2与bax原位杂交进行了观察。结果:再灌注组和黄芪治疗组的梗死面积小于单纯缺血组;DNA电泳发现再灌注组呈凋亡的典型表现,单纯缺血组表现为细胞坏死,黄芪治疗组梯形条带中DNA含量较心肌缺血-再灌注组明显减少;TUNEL染色发现缺血组有散在阳性细胞,再灌注组有大量的阳性标记,且积聚成团,黄芪治疗组较再灌注组明显减少;电镜观察发现再灌注组线粒体等细胞亚结构损伤严重,而黄芪治疗组则明显减轻。缺血组bcl-2与bax表达增多,再灌注组bax表达增多而bcl-2表达减少,黄芪治疗可下调bax且一定程度上调bcl-2。结论:缺血再灌注可引起心肌细胞的凋亡,黄芪可确实抑制凋亡的发生。

Abstract:

Objective: To observe the inhibitory effect of Radix Astragali (Huangqi)on apoptosis induced by myocardial ischemia-reperfusion (I/R). Method: By means of ligature and then repatency of left anterior descending branches coronary artery, the rabbit models with myocardial I/R were established. Myocardial DNA electrophoresis, myocardial apoptosis morphology (TUNEL), ultrastructural organization and in situ hybridization of bcl-2 and bax were observed in different situations. Results: The area of myocardial infarction in ischemia group was larger than that in Radix Astragali group and I/R group. The discovery of DNA electrophoresis in I/R group showed a typical apoptosis. The content of DNA in Radix Astragali group was lower than that in I/R group. The TUNEL staining found a few interspersed apoptosis cells in ischemia group, and the sum of apoptosis cells in I/R group was larger than that in Radix Astragali group. The mitochondria and other organellae injury in the I/R group was more serious than that in Radix Astragali group. The expressions of bcl-2 and bax in ischemia group were increased. The expression of bax was increased, but the expression of bcl-2 was decreased in the I/R group. The expression of bax was down regulated and the expression of bcl-2 was up regulated in Radix Astragali group. Conclusion: The myocardial apoptosis can be induced by I/R and ameliovated by Radix Astragali.