过氧化物酶体增殖物激活受体γ对糖基化终产物诱导大鼠血管平滑肌细胞增殖的作用

Role of peroxisome proliferators activated receptor γ in mediating proliferation of rat vascular smooth muscle cells induced by advanced glycation end products

目的观察吡格列酮对糖基化终产物(AGEs)刺激下大鼠血管平滑肌细胞(VSMCs)增殖的作用及对过氧化物酶体增殖物激活受体γ(PPARγ)基因及蛋白表达水平的影响,探讨PPARγ在AGEs诱导VSMCs增殖中的作用。方法(1)MTT法观察不同浓度、不同时间的AGEs对VSMCs增殖的影响及吡格列酮(1.0、10、100μmol/L)与AGEs共孵育对VSMCs增殖的干预作用。(2)用半定量逆转录聚合酶链反应测定VSMCs中PPARγmRNA的表达。(3)用Western blot法检测PPARγ的蛋白表达。结果AGEs作用导致VSMCs增殖,AGEs抑制PPARγmRNA和蛋白表达水平,这种抑制作用随着AGEs干预的时间延长和浓度的增加而增强(P<0.05)。PPARγ激活剂吡格列酮通过增加PPARγ的表达,抑制AGEs诱导的VSMCs增殖。结论PPARγ表达的下降可能是糖尿病易患动脉粥样硬化的重要原因之一。

Objective To observe the effect of pioglitazone on advanced glycation end products （AGEs）-induced proliferation of vascular smooth muscle cells （VSMCs）and expression of peroxisome proliferators activated receptor γ, （PPARγ）. To investigate the possible role of PPARγ, in mediating AGEs induced proliferation of VSMCs. Methods Primary cultures of smooth muscle cells from rat aorta were exposed to AGEs of different concentrations and different times prior to co-treatment with pioglitazone and AGEs. 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl tetrazolium bromide （MTY） assay was adopted for the quantification of the cell proliferation ratio and PPARγ, expression was determined by RT-PCR and Western immunblotting. Results AGEs increased the proliferation of VSMCs. AGEs treatment to VSMCs decreased mRNA and protein levels of PPARγ, in a time- and dose-related manner （ P 〈 0. 05）. Pioglitazone inhibited the AGEs-induced proliferation of VSMCs in vitro. Conclusions Activating PPARγ, in VSMCs, pioglitazone may play a role in antiatherosclerosis. The reduction in PPARγ, expression may be implicated in vascular smooth muscle cells proliferation and pathogenesis of atherosclerosis in patients with diabetes mellitus.