单侧输尿管结扎对大鼠肾间质PI3K/AKT表达的影响  

Changes of PI3K/AKT expression in renal tubulointerstitial fibrasis of unilateral ostruction rats

作　　者：彭红霞[1] 陈明[1] 张超[1] 欧三桃[1] 刘斌[1] 

机构地区：[1]泸州医学院附属医院肾内科肾功能保护研究室

出　　处：《基础医学与临床》2006年第12期1345-1349,共5页Basic and Clinical Medicine

基　　金：四川省教育厅2004年重点资助课题(2000128;2004049)

摘　　要：目的探讨PI3K/AKT信号通路是否参与肾间质纤维化的发病过程。方法将30只SD大鼠随机分为假手术组、UUO模型组,模型组行左侧输尿管结扎术。术后5、10和15 d分别处死各组中的5只大鼠,取左肾行HE和Masson染色,并用免疫组化方法检测肾小管-间质中TGF-β1、AKT1、磷酸化AKT1的表达。结果模型组大鼠肾小管-间质细胞增多,肾小管基底膜增厚皱缩,纤维化明显,随时间进展而加重。不同时间的UUO模型组肾组织AKT1、磷酸化AKT1、TGF-β1表达显著高于假手术组(P<0.01);于第10天模型组AKT1表达达高峰,于第15天磷酸化AKT1、TGF-β1表达达高峰;UUO大鼠肾组织第5天和第15天TGF-β1的表达与AKT1活性呈正相关,第10天和第15天梗阻肾的AKT1活性与肾小管-间质纤维化指数呈正相关(均P<0.05)。结论AKT1、磷酸化AKT1在大鼠梗阻性肾病模型肾小管-间质中表达及AKT1活性明显增加,提示PI3K/AKT信号通路可能参与肾小管-间质纤维化的过程。Objective To observe the effect of PI3K/AKT signal passageway on renal tubulointerstitial fibrogenesis of UUO rats. Methods Thirty Sprague Dawley rats were divided into two groups, the sham-operated group and the uuo model group. The model group＇ s left ureter was dissociated to be obstructed. The sham-operated group was dissociated left ureter only without obstruction. Five rats of each group were killed respectively at 5, 10, 15 days after surgery. Histological changes of renal tubular interstitium was observed by HE and Masson staining. Immunohistochemistry was performed on left renal tubular interstitium for AKT1, phospho-AKT1, TGF-β1 in renal tubulointerstitum at each time point. Results AKT1 ,phospho-AKTland TGF-β1 were faintly stained in the sham- operated kidneys. Immunostaining of AKT1, phospho-AKT1 and TGF-β1 in renal tubulointerstitium increased progressively starting from 5 to 15 days after UUO （ vs sham-operated group, P 〈 0. 01 ）. the activity of AKT1 is positive correlation with expression of TGF-β1 early and later after UUO （P 〈 0. 05 ）and is also positively correlated to fibrosis index of renal tubulointerstitium from 10 to 15 days after UUO （P 〈 0. 05 ）. Conclusion After UUO,Increasing of protein expression of phospho-AKT1 and AKT1 in renal tubulointerstitium, and enhancing of activity of AKT1 concerned with TGF-β1 induced renal tubulointerstitial fibrosis,Thus, PI3K/AKT signal passageway may play roles in renal tubulointerstitial fibrogenesis in unilateral ureteral obstruction rats.

关 键 词：PI3K/AKT信号通路 TGF-Β1 肾小管-间质纤维化 

分 类 号：R692[医药卫生—泌尿科学]