吡格列酮对高脂血症大鼠主动脉内皮细胞凋亡的作用

Effect of pioglitazone on aortic endothelial cell apoptosis in hyperlipidemic rats

目的观察吡格列酮对高脂血症大鼠主动脉内皮细胞凋亡的影响,并探讨其可能的作用机制。方法清洁型SD大鼠26只,随机分为健康对照组(9只)、高脂饮食组(17只),高脂饮食组喂养12周后再随机分为模型组(8只)和吡格列酮组(9只),4周后,检测各组血脂水平,通过免疫组织化学法检测主动脉Bcl-2、Bax的表达,TUNEL染色法观察主动脉内皮细胞凋亡情况,计算细胞凋亡指数。结果 (1)高脂饮食组喂养12周后,血脂明显升高;给药4周后,与模型组比较,吡格列酮组TG、TC水平明显降低(P=0.000);(2)与健康对照组相比,模型组主动脉Bax蛋白表达明显增高(P=0.003),Bcl-2蛋白表达和Bcl-2/Bax比值明显降低(P=0.000);与模型组相比,吡格列酮组主动脉Bax蛋白表达明显降低(P=0.000),Bcl-2蛋白表达(P=0.001)和Bcl-2/Bax比值明显升高(P=0.000),且吡格列酮组主动脉内皮细胞凋亡指数较模型组明显降低,差异有统计学意义(17.5633±7.0584比6.0475±2.2370,P=0.000)。结论吡格列酮可改善高脂血症大鼠血脂水平,调节凋亡蛋白表达,减少主动脉内皮细胞凋亡。

Objective To investigate the influence of pioglitazone on aortic endothelial cell apoptosis in hyper]ipidemia rats and its possible mechanism. Methods A total of 26 male SD rats were randomly divided into control group （n = 9 ） and high-fat diet group （n = 17 ）. Rats at high-fat diet group raised for 12 weeks were randomly devided into model group （n = 8 ） and pioglitazone treatment group （n = 9 ）. After 4 weeks, serum lipid level of all rats was measured and apoptosis protein expression of Bax and Bcl-2 on the aorta was analyzed by immunohistochemical method. Terminal deoxynucleotidyl transferase- mediated dUTP nick end labeling was used to observe apoptotic cells in aortic intimal area and to calculate apoptosis index. Results （ 1 ） Serum levels of TG and TC were significantly higher in model group and pioglitazone treatment group than in control group. Serum levels of TG and TC were significantly decreased in pioglitazone treatment group than in model group （ P = 0. 000 ）. （ 2 ） Compared with control group, the expression of Bax protein on aorta was significantly increased （ P = 0. 003 ） and the Bcl-2 protein and ratio of Bcl-2/Bax were markedly decreased in model group （P = 0. 001 and 0. 000, respectively）. The expression of Bax protein was significantly lower and Bcl-2 protein and ratio of Bcl-2/Bax were significantly higher in pioglitazone treatment group than in model group, and apoptotic index of aortic intima was significantly lower than in model group [ （ 17. 5633 ± 7.0584 ） vs. （ 6. 0475 ±2. 2370 ）, P = 0. 000 ] . Conclusions Pioglitazone can regulate the expression of apoptosis endothelial cell apoptosis in hyperlipidemia rats.