辛伐他汀通过上调动脉粥样硬化大鼠血管壁Bcl-2蛋白的表达而抑制细胞凋亡

Effects of simvastatin on aortic vascular endothelial cell apoptosis and Bcl-2 protein expression in a rat model of atherosclerosis

目的探讨辛伐他汀对动脉粥样硬化(AS)大鼠模型血管壁细胞凋亡、Bcl-2蛋白的表达干预作用。方法高脂饲料及腹腔注射维生素D_3复制大鼠AS模型,随机分为对照组(n=10)给予普通饲料喂养,实验组(n=13)给予高脂饲料喂养,干预组(n=13)给予高脂饲料喂养基础上加用辛伐他汀干预,11周后取胸主动脉,观察其斑块变化。采用免疫组化Elivision法测定AS血管壁中Bcl-2蛋白表达。通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)法检测细胞凋亡指数(AI),分析各组中Bcl-2表达及AI变化。结果与对照组比较,Bcl-2蛋白的表达在实验组明显降低(P<0.05);而与实验组比较,干预组Bcl-2蛋白的表达明显升高(P<0.05),且与对照组比较无差异。同时,AI在各组中的变化比较则相反,差异均有统计学意义(P<0.05)。结论辛伐他汀抗大鼠AS的作用可能与上调Bcl-2蛋白表达,进而抑制细胞凋亡相关。

Objective To explore the effects of simvastatin on vascular endothelial cell apoptosis and Bcl-2 protein expression in the aorta in a rat model of atherosclerosis. Methods Thirty-six rats were randomized into control group(n=10), atherosclerosis model group(n=13) and simvastatin intervention group(n=13). In the latter two groups, rat models of atherosclerosis were established by intraperitoneal injection of vitamin D3 combined with high-fat feeding for 6 weeks, and the control rats were fed with regular diet. In the intervention group, the rats were further fed with high-fat diet with daily simvastatin treatment for 4 weeks. After the treatments, the pathological changes and plaque in the thoracic aorta were observed, and the expression of Bcl-2 protein was detected with immunohistochemistry. TUNEL assay was used to determine the apoptosis index(AI) of the vascular endothelial cells. Results Compared with that in the control group, Bcl-2 protein expression in the aorta of atherosclerotic rats was significantly decreased(P<0.05); simvastatin treatment obviously increased the expression of Bcl-2 protein in atherosclerotic rats(P<0.05) to a level similar to that in the control group. The AI was the highest in the model group(P<0.05) and comparable between the control and simvastatin treatment group. Conclusion The therapeutic effect of simvastatin against atherosclerosis is probably mediated by up-regulation of Bcl-2 protein, which inhibits vascular endothelial cell apoptosis in rats with aortic atherosclerosis.