过氧化物酶体增殖物活化受体γ激动剂对肾病大鼠肾组织nephrin表达的调控  

Transcriptional Regulation of nephrin Gene by Peroxisome Proliferator-Activated Receptor γ Agonist in Nephridial Tissue in Nephropathy Rats

作　　者：丁桂霞[1] 黄松明[2] 张爱华[2] 费莉[3] 郭梅[3] 潘晓勤[3] 陈荣华[3] 

机构地区：[1]南京医科大学第二附属医院儿科,南京210011 [2]南京医科大学附属南京市儿童医院,南京210008 [3]南京医科大学儿科医学研究所,南京210029

出　　处：《实用儿科临床杂志》2006年第19期1314-1316,共3页Journal of Applied Clinical Pediatrics

基　　金：国家自然科学基金项目资助(30100081);江苏省自然科学基金项目资助(BK2004144);江苏省教育厅基金项目资助(04KJB320083)

摘　　要：目的探讨过氧化物酶体增殖物活化受体γ(PPARγ)对nephrin表达的调控作用。方法建立大鼠氨基核苷嘌呤霉素(PAN)肾病模型,应用实时定量PCR和免疫印迹法检测肾病大鼠不同时间点肾组织中PPARγ和nephrin mRNA和蛋白表达,并观察PPAR-γ激动剂罗格列酮大鼠肾组织中nephrin表达的影响。体外培养HEK293细胞,转染含荧光素酶报告基因的nephrin启动子区,观察罗格列酮对nephrin基因转录活性的影响。结果PAN肾病模型d1 PPARγ、nephrin mRNA和蛋白即出现下降,d3出现明显下降,d7下降到最低点,PPARγ与nephrin表达呈显著正相关,而PPARγ和nephrin蛋白表达与24 h尿蛋白排泄呈负相关;罗格列酮治疗后大鼠尿蛋白排泄明显下降,肾组织中nephrin表达回升;罗格列酮呈时间依赖性诱导nephrin基因的转录活性,3 h达高峰,其后荧光素酶活性有所下降,但刺激24 h仍显著高于对照组。结论nephrin表达受PPARγ调控,PPARγ激动剂通过诱导nephrin表达而减轻蛋白尿。Objective To investigate the effect of peroxisome proliferator activated receptor γ（PPARγ） agonist on the transcriptional regulation of ncphrin gene. Methods The model was established by a single injection of puromycin aminonucleoside （PAN）. Urine protein excretion was determined by Bradford method. The expressions of PPARγ nephrin mRNA and protein wcrc dctermined by real time time polymerase chain reaction（PCR） and immunoblotting. HEK293 cells were transfected with plasmids that harbor the luciferase gene under portions of human nephrin gene promoter and stimulated with rosiglitazone （ 10 μmol/L）. Results The expression of PPARγ, nephrin rnRNA and protein was significantly down regulated with the progression of proteinuria in PAN nephropathy rats. Rosiglitazone reduced proteinuria and restored nephrin mRNA and protein expression. Rosiglitazone significantly increased the transcriptional activity of luciferase gene. Conclusion PPARγ ligand rosiglitazone induces nephrin gene transcription through specific peroxisome proliferator responsive element（PPRE） in its promoter.

关 键 词：氧化物酶体增殖物活化受体γ NEPHRIN 氨基核苷嘌吟霉素肾病 蛋白尿 

分 类 号：R692[医药卫生—泌尿科学]