过氧化体增殖物激活型受体激活物对HepG-2细胞PAI-1表达的影响

EFFECT OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS ACTIVATORS ON PLASMINOGEN ACTIVATOR INHIBITOR-1 EXPRESSION IN HEPG-2 CELLS

目的 :观察不同的过氧化体增殖物激活型受体 (peroxisomeproliferator activatedreceptors,PPARs)激活物对HepG 2细胞纤溶酶原激活物抑制剂 1 (plasminogenactivatorinhibitor 1 ,PAI 1 )mRNA表达及其活性的影响 ,探讨过氧化体增殖物激活型受体在PAI 1基因调控中的作用。方法 :分别利用硬脂酸、油酸、亚油酸、非诺贝特、吡格列酮作为诱导因素刺激HepG 2细胞 ,采用半定量RT PCR法检测PAI 1mRNA及PPARsmRNA的转录水平 ,比色法检测PAI 1活性变化 ,Westernblot法检测PPARs蛋白表达情况。结果 :与对照组比较 ,油酸、亚油酸组HepG 2细胞PAI 1mRNA表达及蛋白活性显著增加 ;非诺贝特组HepG 2细胞PAI 1mRNA表达及活性显著降低 ;硬脂酸、吡格列酮组HepG 2细胞PAI 1mRNA表达及蛋白活性均无显著变化 ;各组PPARs在mRNA及蛋白水平均无明显差异。结论 :PPARs激活物对HepG 2细胞PAI 1mRNA表达及其活性具有调节作用 ,PPARα可能是实现该调节作用的重要途径之一 ,同时不排除其他调控因素介入该调节过程。

Aim: To investigate the effect of different peroxisome proliferator activated receptors(PPARs) activators on plasminogen activator inhibitor 1 in HepG 2 cell line and explore the effect of PPARs on PAI 1 gene expression. Methods: Stearic acid, oleic acid, linoleic acid, fenofibrate, pigolitazone were used in the treatment of HepG 2 cell culture. The level of PAI 1 and PPARs mRNA was measured by reverse transcription polymerase chain reaction(RT PCR) and the level of PAI 1 activity and PPARs protein was deter mined by colorimetric assay and western blotting respectively. Results: The mRNA and activity of PAI 1 significantly increased in the groups of oleic acid and linoleic acid compared with the control, but decreased in the group of fenofibrate. There were no significant changes in both groups of stearic acid and pioglitazone. The alterations in the level of PPARs mRNA and protein were not detected in all the treated groups compared with the control. Conclusion: Peroxisome proliferator activated receptors activators play important roles in the PAI 1 gene expression and regulation. It is likely mediated by the activation of PPARα, but there might be other mechanisms.