中文摘要：

目的探讨过氧化物酶增殖物激活受体（PPAR）γ1对血管紧张素Ⅱ（AngⅡ）诱导的系膜细胞外基质积聚的抑制作用及其机制。方法脂质体转染质粒pIRES2-EGFP-PPARγ1／WT（野生型）于系膜细胞，给予AngⅡ（10^-7mol／L）刺激48h。采用RT-PCR检测TGF-β1、PAI-1、c-fos、c-jun mRNA表达水平。采用ELISA法检测细胞上清液中TGF-β1和FN浓度。Western印迹观察胞浆中I-κB、NF—κB及胞核中NF-κB、pERK蛋白表达水平。利用PPARγ与PPRE结合活性测定PPARγ1在系膜细胞中的活性。同时以PPARγ激动剂吡格列酮（6μmol／L）、不具有目的基因PPARγ1的空白质粒pIRES2-EGFP和表达功能缺陷．突变型（DN）PPARγ1的质粒pIRES2-EGFP—mPPARγ1／DN作为对照。结果PPARγ1过表达能显著性抑制AngⅡ诱导的系膜细胞TGF—β1、PAI-1的mRNA高表达（P〈0．05），同时下调c-fos和c-jun mRNA高表达（P〈0．05）。转染PPARγ1／WT能显著降低AngⅡ48h刺激下细胞上清液中FN和TGF-β1浓度（P〈0．05）。在AngⅡ作用下系膜细胞AT1表达增加（P〈0．05），PPARγ1可显著性减少AT1的高表达（P〈0．05）。AngⅡ诱导的系膜细胞pERK表达明显升高，PPARγ1可显著性减少pERK表达（P〈0．05）。转染PPARγ1／WT能上调AngⅡ刺激下系膜细胞胞浆中I-κB低表达，同时下调NF-κB由胞浆向细胞核的转移（P〈0．05）。转染PPARγ1／DN并无上述作用。吡咯列酮具有与PPARγ1相同的显著性效应。PPARγl／WT转染组PPARγ1的活性明显高于其他组（P〈0．05）。结论PPARγ1过表达能够抑制AngⅡ刺激下系膜细胞外基质的聚积，降低ATl受体蛋白表达．具有直接抗硬化的非代谢性效应，其机制可能是通过抑制ERK／AP-1及NF-κB等信号分子的传递。

英文摘要：

Objective To study the inhibitive effect and mechanism of PPARγ1 on the extracellular matrix （ECM） accumulation of mesangial cells induced by Ang Ⅱ .Methods The plasmid of PPARγ1/WT （wild type） was transfected into mesangial cells. After 48 hours of Ang Ⅱ stimulation, the gene expression of TGF-β1, PAI-1, c-los and c-jun was examined by RT-PCR. Protein levels of p-ERK, I-κB and nucleus/cytosol ratio of NF-κB were estimated by Westen-blot. The concentrations of FN and TGF-β1 were estimated by ELISA. The activity of PPARγ1 was examined by specific PPRE binding activity. Plasmid expressing non-functional dominant negative type of mPPARγ1, pIRES2-EGFP-mPPARγ1/DN （DN）, and blank plasmid, pIRES2-EGFP （Blank） were used as controls. Effects of 6 μmol/L PPARγ agonist pioglitazone （Pio） were also studied. Results The expression of TGF-β1 and PAI-1 mRNA in mesangial ceils induced by Ang Ⅱ was inhibited by PPARγ1 （P 〈 0.05）. The over-expression of PPARγ1 down-regulated the expression of c-fos and c-jun significantly （P 〈 0.05）. The expression of AT1 was enhanced by Ang Ⅱ , whereas it was significantly inhibited by the PPARγ1 （P〈0.05）. FN and TGF-β1 production were decreased by PPARγ1/WT transfection. PPARγ1 significantly up-regulated the low-expressed I-κB of cytoplasm and down-regulated the transfer of NF-κB from cytoplasm to nuclear by Ang Ⅱ （P 〈0.05）. PPARγ1/DN did not show the above effects. Pioglitazone had the same effects as PPARγ1 on these parameters in mesangial cells when treated with AngⅡ medium（P 〈 0.05）. The activity of PPAR1γ in the PPARγ1/WT transfected group was significantly higher than that in other groups （P 〈 0.05）. Conclusions PPARγ1 inhibits ECM accumulation induced by Ang Ⅱ through suppressing the expression of AT1, which involves its inhibitory effects on activation of ERK/AP-1 and NF-κB pathways.