PPARα对糖基化终产物诱导的大鼠血管平滑肌细胞的作用  

Role of Peroxisome Proliferators Activated Receptor Alpha in Mediating Proliferation of Rat Vascular Smooth Muscle Cells Induced by Advanced Glycation End Products

作　　者：魏礼清[1] 汪炳华[2] 黄丽丽[2] 秦欢[2] 

机构地区：[1]武汉市中心医院检验科,湖北武汉430014 [2]武汉大学医学院生物化学与分子生物学系,湖北武汉430071

出　　处：《武汉大学学报（医学版）》2008年第6期707-711,共5页Medical Journal of Wuhan University

基　　金：湖北省卫生厅基金资助课题(编号:301140469)

摘　　要：目的:观察氯贝特对糖基化终产物(AGEs)刺激下的离体大鼠主动脉血管平滑肌细胞(VSMCs)增殖的作用以及对过氧化物酶体增生物激活受体α(PPARα)基因及蛋白表达水平的影响,探讨PPARα在AGEs诱导VSMCs增殖中的作用。方法:体外培养大鼠VSMCs,应用不同浓度的AGEs分别刺激VSMCs并设立对照组进行比较,采用MTT法观察不同浓度的AGEs对VSMCs增殖的影响及氯贝特与AGEs共孵育对VSMCs增殖的干预作用,并用流式细胞仪检测细胞周期,RT-PCR检测PPARα的mRNA表达,Western blotting分析PPARα的蛋白表达。结果:AGEs增加DNA的合成促进平滑肌细胞的增殖,氯贝特激活PPARα,使PPARα的表达量增加,抑制AGEs诱导的细胞增殖和DNA合成。结论:AGEs诱导平滑肌细胞增殖与平滑肌细胞PPARα表达相关,PPARα表达下调可能是产生糖尿病动脉粥样硬化的重要原因之一。Objective： To observe the effect of clofibrate on advanced glycation end products （AGEs） induced proliferation of vascular smooth muscle cells （VSMCs） and expression of peroxisome proliferators activated receptor alphα （PPAR α）, and to investigate the possible role of PPAR α in mediating AGEs induced proliferation of VSMCs. Methods： Primary cultured smooth muscle cells from rat aorta were exposed to AGEs at different concentrations prior to co-treatment with clofi- brate. MTT assay was adopted for the quantification of the cell proliferation ratio and cell cycle was tested with flow cytometry, the mRNA expression level of PPARαwere detected by RT- PCR, and the PPARα protein were detected by Western blotting. Results： AGEs increased the proliferation of VSMCs, the mRNA and protein expression level of PPAR a were increasing induced by clofibrate, and the AGEs-induced proliferation of VSMCs were inhibited in vitro （P〈 0.05）. Conclusion. Proliferation of rat VSMCs induced by AGEs is bound up with that of PPAR α expression in VSMCs, and the reduction in PPARα expression may be implicated in the pathogenesis of atherosclerosis in patients with diabetes mellitus.

关 键 词：PPARΑ 血管平滑肌细胞 氯贝特 晚期糖基化终产物 细胞增殖 

分 类 号：R587.1[医药卫生—内分泌]