内皮素-1刺激对血管平滑肌过氧化物酶体增殖物激活受体γ表达的作用

摘要/Abstract

摘要： 目的研究ET-1对血管平滑肌过氧化物酶体增殖物激活受体γ(PPAR-γ)表达的影响以及与血管平滑肌增殖的关系。方法以成年16周Wistar大鼠为研究对象,采用主动脉血管平滑肌原代培养技术,培养大鼠腹主动脉血管平滑肌1~3代,然后加入ET-1进行刺激,使用RT-PCR和Westernblot技术观察ET-1作用后0、12、24、48、72h以及不同浓度ET-1刺激48h后PPAR-γmRNA和蛋白表达变化,同时用MTT法检测血管平滑肌(VSMCs)增殖。结果 ET-1刺激后12h,PPAR-γ在mRNA和蛋白水平表达上未见明显变化(P>0.05),而24h时出现了表达轻度下调,与对照组(无ET-1刺激)差异具有显著性(P<0.05),48~72h下降更加明显,与对照组相比差异具有高度显著性(P<0.01)。不同浓度ET-1刺激48h后,随着浓度的增加,PPAR-γ表达减低,各组相比具有显著性差异(P<0.01)。而血管平滑肌的增殖在12h就出现,且随着时间的延长,增殖增强。而且随着ET-1浓度的增加,VSMCs增殖增加。结论 ET-1在引起VSMCs增殖的同时,可引起PPAR-γ在mRNA和蛋白水平的表达减低,提示ET-1导致的VSMCs增值可能与PPAR-γ有一定的关系。

Abstract: Objective To investigate the effect of endothelin-1 (ET-1) on the expression of peroxisome proliferators-activated receptor-γ in vascular smooth muscle cells. Methods The first to the third passages of aortic vascular smooth muscle cells (VSMCs) isolated from 16-week-old Wistar rats were cultured in vitro and stimulated by ET-1 for 12, 24, 48, and 72 h, respectively, and at different concentrations of ET-1 for 48 h. PPAR-γ mRNA expression of the cells was detected by reverse transcription (RT)-PCR and PPAR-γ protein by Western blotting after the stimulations, and the proliferation of VSMCs was evaluated by MTT assay. Results No changes in PPAR-γ mRNA and protein expressions were observed in the VSMCs after ET-1 stimulation for 12 h (P>0.05), and when the stimulation was prolonged to 24 h, slight decrease in the expressions occurred but the difference was not statistically significant in comparison with the control group (P<0.05). After 48 to 72 hour’s ET-1 stimulation, the expressions of both PPAR-γ mRNA and protein were markedly decreased as compares with the control group (P<0.01). The expressions of PPAR-γ in mRNA and protein were both decreased with the increase of ET-1 concentration after stimulation for 48 h. VSMC proliferation occurred at 12 h during ET-1 stimulation and increased with time and ET-1 concentration. Conclusion ET-1 stimulation can induce VSMC proliferation and decrease the expressions of both PPAR-γ mRNA and protein.

中图分类号:

R543

狄政莉¹, 牛小麟¹, 魏瑾¹, 高登峰¹, 汪南平². 内皮素-1刺激对血管平滑肌过氧化物酶体增殖物激活受体γ表达的作用[J]. 南方医科大学学报, 2005, 25(09): 1140-1144.

DI Zheng-li¹, NIU Xiao-lin¹, WEI-Jin¹, GAO Deng-feng¹, WANG Nan-ping². Effect of endothelin-1 stimulation on peroxisome proliferator-activated receptor-γ expression in vascular smooth muscle cells[J]. Journal of Southern Medical University, 2005, 25(09): 1140-1144.

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