瑞舒伐他汀对心肌缺血再灌注损伤大鼠 心肌凋亡及相关基因表达的影响

Effect of Rosuvastatin on myocardial cell apoptosis in rat model of myocardial ischemia reperfusion injury

摘要:

目的 探讨瑞舒伐他汀对心肌缺血再灌注损伤（MIRI）大鼠心肌细胞凋亡及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）、心肌缺血再灌注组（MIRI 组）、心肌缺血再灌注+ 瑞 舒伐他汀组（MIRI+R 组），每组10 只。复制大鼠MIRI 模型，观察各组大鼠左心室舒张末压（LVEDP），左 心室内压最大上升和下降速率（±dp/dtmax）；脱氧核糖核苷酸末端转移酶介导的缺口末端标记法检测大鼠 左心室心肌细胞的凋亡指数；免疫组织化学染色检测左心室心肌组织凋亡相关基因（Bcl-2、Bax）蛋白表达， RT-PCR 法检测Bcl-2、Bax mRNA 表达。结果 MIRI 组与Sham 组比较，大鼠LVEDP、心肌细胞凋亡指 数（AI）、Bax 蛋白及mRNA 的表达升高（P <0.05），±dp/dtmax、Bcl-2 蛋白及mRNA 的表达、Bcl-2/Bax 比值下降（P <0.05）；与MIRI 组比较，MIRI+R 组大鼠LVEDP、AI、Bax 蛋白及mRNA 的表达降低（P <0.05）， ±dp/dtmax、Bcl-2 蛋白及mRNA 的表达、Bcl-2/Bax 比值升高（P <0.05）。结论 瑞舒伐他汀可降低心肌缺 血再灌注损伤引起的心肌细胞凋亡，具有良好的心肌保护作用。

Abstract:

Objective To investigate the effect of Rosuvastation on myocardial cell apoptosis and apoptosisassociated genes expression in rat model of myocardial ischemia reperfusion injury (MIRI). Methods MIRI model was constructed based on standard procedure. Rat in Sham group received all procedures except for myocardial infarction and reperfusion. Rosuvastation was administrated in treatment group. Hemodynamic parameters including LVEDP and ±dp/dtmax were recorded. Cellular apoptotic index (AI) of left ventricular was measured by TUNEL staining. Apoptotic related Bcl-2 and Bax were measured by Immunohistochemistry and RT-PCR. Results Rats in MIRI group experienced increased levels of LVEDP, AI and Bax and decreased levels of ±dp/dtmax and Bcl-2 when compared with Sham group (P < 0.05). All the mentioned alteration of apoptotic status were reversed by treatment of Rosuvastationin MIRI+R group compared with MIRI group (P < 0.05). Conclusion Rosuvastatin exerts myocardial protection through downregulation of cell apoptosis in rat model of myocardial ischemia reperfusion injury.