目的:观察新型PPARγ激动剂DH9对人多囊肾囊肿衬里上皮细胞(WT9-12)增殖的影响.方法:予以不同浓度的DH9及罗格列酮作用WT9-12细胞24、48、72、96 h,MTT法检测细胞增殖情况;流式细胞术观察细胞周期的改变;AnnexinV+PI双染色流式细胞术测定细胞凋亡率;Western blotting分析cyclinA、P21CIP/WAF1、Bax和Bcl-2的表达.结果:DH9抑制细胞增殖作用明显优于罗格列酮(P＜0.05),并呈量-效和时-效关系.比较加入PPAR-γ抑制剂GW9662前后细胞增殖抑制作用差异无统计学意义(P>0.05).DH9可增加P21CIP/WAF1蛋白合成,减少CyclinA蛋白合成,使细胞阻滞在S期.DH9作用72 h后Bcl-2/Bax的比值分别为较对照组(2.19±0.08)显著减少(P＜0.05),具有促进细胞凋亡的作用.结论:DH9抑制WT9-12细胞增殖活性明显优于罗格列酮,且这种增殖抑制作用与DH9作用在细胞周期的不同调节点,促进WT9-12细胞凋亡有关.%Objective: To investigate the effects of a novel PPAR-y agonist DH9 on the proliferation in human polycystic kidney cyst - lining epithelial cells. Methods: The cyst - lining epithelial cells( WT9 - 12 )from human polycystic kidney were treated with DH9 and/or rosiglitazone for 24、48、72、96 hours with or without GW9662. The proliferation was assessed by MTT. Cell cycles were analyzed by flow cytometry. The cyclinA、P21CIP/WAF1 ^Bax and Bel -2 were detected by Western blotting. Results :DH9 could effectively inhibit the proliferation of the cells through S cell cycle. DH9 could downregulate the expression of cyclinA and upregulate the expression of P21CIP/WAF1. DH9 could induce apoptosis through Bel -2/ Bax pathway. Conclusion: DH9 can more effectively block the proliferation of cyst - lining epithelial cells independent of PPAR-y. The effect may be mediated by blocking the cell cycle and induce apotisis.
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