霉酚酸酯对UUO大鼠肾间质TGF-β_1、PAI-1表达的影响  

Effects of MMF on Expression of TGF-β_1 and PAI-1 in Rats After Unilateral Ureteral Obstruction

作　　者：彭琳[1] 张浩[1] 唐静[2] 张显明[1] 

机构地区：[1]中南大学湘雅三医院肾内科,长沙410013 [2]南华大学附属南华医院肾内科,湖南衡阳421002

出　　处：《实用临床医学（江西）》2007年第5期1-4,共4页Practical Clinical Medicine

基　　金：湖南省自然科学基金项目(05JJ30059)

摘　　要：目的:通过霉酚酸酯(MMF)干预单侧输尿管梗阻(UUO)模型大鼠,动态观察转化生长因子-β1(TGF-β1)、纤溶酶原激活抑制物-1(PAI-1)在梗阻侧肾组织中的表达,探讨MMF延缓肾间质纤维化进展的机制。方法:将54只大鼠随机分为假手术组、单侧输尿管结扎手术组和霉酚酸酯组。采用UUO模型,在术后7 d1、4 d、21 d每组各取6只处死,留取梗阻侧肾组织行HE染色,观察肾脏病理学变化,并用免疫组化方法测定肾组织中TGF-β1、PAI-1的表达变化。结果:MMF能改善UUO所致的肾间质损伤和肾间质纤维化程度(第7天、14天P<0.01;第21天P<0.05);降低肾脏组织TGF-β1蛋白的表达(P<0.01);减少TGF-β1下游致纤维化因子PAI-1蛋白的表达(P<0.05)。结论:MMF能保护UUO所致的肾间质炎症和纤维化损伤。其作用机制可能为通过减少TGF-β1表达,抑制TGF-β1下游效应因子PAI-1的表达,从而抑制肾间质纤维化。Objective：To investigate the mechanism of renal interstitial fibrosis after unilateral ureteral obstruction and the renoprotective effect of MMF. Methods： Fifty--four rats were randomly assigned to shame operation group, operation group and MMF（15mg · kg^-1 ·d^- 1）treatment group after unilateral ureteral obstruction. Renal tissues were examined by HE stain. Immunhistochemistry was performed for transforming growth factor -β1 （TGF -β1 ）, plasminogen activator inhibitor-1（PAI-1） in the renal interstitum. Results： The fibrosis index of the UUO group was significantly increasedand the fibrosis in＇dex values of MMF group was significantly lower than that of the UUO group （Seven days and Fourteen days P〈0.01, Twenty-one da-ys P〈0.05）. TGF-β1 protein was highly expressed in the UUO group, however, the expression of TGF-β1 protein level in the MMF group was significantly lower, in com-parison with the UUO group （P〈0. 01）. The PAI-1 protein expression of the UUOgroup was significantly higher （P〈0.01）, however, the PAI-1 protein expression of the MMF group was significantly lower than that of the UUO group （P〈0.05）. Conclusion： MMF inhibits the renal interstitial macrophage infiltration, down-regulates the expression of the downstream target genes, thus blocking the renal fibrosis.

关 键 词：霉酚酸酯 肾间质纤维化 TGFΒ1 PAI-1 

分 类 号：R-332[医药卫生]