糖尿病肾病大鼠肾脏纤维化逆转可能性的研究  

Study on the possibility of renal fibrosis reverse in diabetic nephropathy rats

作　　者：方开云[1] 娄晶磊[1] 肖瑛[1] 石明隽[1] 桂华珍[1] 郭兵[1] 张国忠[1] 

机构地区：[1]贵阳医学院病理生理学教研室,贵州贵阳550004

出　　处：《中国老年学杂志》2009年第10期1208-1212,共5页Chinese Journal of Gerontology

基　　金：教育部高等学校博士学科点专项科研基金(20060660001);贵州省省长基金(2005-303)

摘　　要：目的动态观察α-平滑肌肌动蛋白(α-SMA)和E-钙黏素(E-cadherin)在糖尿病(DM)大鼠肾组织中的表达,探讨糖尿病肾病(DN)大鼠肾脏纤维化逆转的可能性。方法选择SD大鼠随机分为正常对照组、DM组和胰岛素治疗组,链脲佐菌素(STZ)诱发大鼠DM。正常对照组和DM组按病程分为2、4、8、12、16、20和24 w组,胰岛素治疗组从第13周起用胰岛素控制血糖至正常水平,分为16、20和24 w组。检测各组血糖、24 h尿蛋白、血肌酐(Scr)和肾脏指数(RI);PAS染色光镜观察肾脏病理改变;免疫组化检测肾皮质α-SMA和纤连蛋白(FN)的表达;Western印迹检测肾皮质α-SMA和E-cadherin蛋白表达量;RT-PCR检测肾皮质α-SMA和FN mRNA水平。结果DM组大鼠血糖、24 h尿蛋白、Scr、RI均较正常对照组明显升高(P<0.05,P<0.01),胰岛素治疗组上述指标均较DM组显著降低(P<0.05,P<0.01)。正常大鼠α-SMA只在血管壁表达,DM组2 w开始有少量间质细胞胞浆内有阳性染色,随病程进展间质细胞阳性染色增多;8 w时肾小球系膜细胞胞浆内见阳性表达;从16 w开始在DM大鼠肾小管上皮细胞可见α-SMA蛋白阳性表达,胰岛素治疗组未见表达;DM组肾皮质α-SMA和FN蛋白与mRNA表达水平较正常对照组显著增多(P<0.01),胰岛素治疗组则显著低于DM组(P<0.01);DM组E-cadherin蛋白的表达水平较正常对照组显著降低(P<0.01),而胰岛素治疗组显著高于DM组(P<0.01)。结论控制血糖可使DN大鼠肾脏一定程度的纤维化逆转,其机制可能与肾脏固有细胞表型转变被抑制或反转有关。Objective To dynamic observe the expressions of α-smooth muscle actin （α-SMA） and E-cadherin to investigate the possibility of renal fibrosis reverse in diabetic nephropathy rats. Methods Streptozotocin-induced diabetic rats were randomly divided into 2,4,8,12,16,20,24 w and 16,20,24 w treatment groups. The treatment groups were treated with insulin to control blood glucose to normal level beginning from the 13 th week. Normal control groups were selected in age-matching points respectively. Blood glucose, 24 h urine protein, serum ereatinine （Scr）, renal index（RI） of rats were measured. PAS staining was used to observe the renal pathological changes. Immunohistoehemieal staining, Western blotting and RT-PCR were employed to determine the expressions of α-SMA, E-eadherin and fibronectin （FN）. Results Compared with control group and insulin-treated rats, blood glucose, 24 h urinary protein excretion, Scr, and RI were increased remarkably in diabetic rats （ P 〈 0. 05, P 〈 0.01 ）. In diabetic rats, interstitial, mesangial cells and tubule stainings of α-SMA were seen at the 2, 8 and 16 th week respectively. The α-SMA and FN protein and mRNA were significantly up-regulated in diabetic rats, while down-regulated in the insulin-treated diabetic rats （ P 〈 0. 01 ）. The expression of E-cadherin protein in the cortex was contrary to the expression of α-SMA. Conclusions Renal fibrosis at early stage in diabetic nephropathy rats can be reversed when blood glucose was controlled and the mechanism may involve in blocking or reversing the phenotypic transition of renal resident cells.

关 键 词：Α-平滑肌肌动蛋白 E-钙黏素 糖尿病.肾病 大鼠 

分 类 号：R363[医药卫生—病理学]