糖尿病大鼠肾小管BMP-7和p38MAPK表达关系的研究  

Study on relationship of expression among BMP-7 and p38MAPK in renal tubules of diabetic rats

作　　者：肖瑛[1] 方开云[1] 石明隽[1] 刘瑞霞[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：《中国现代医学杂志》2009年第16期2417-2421,2425,共6页China Journal of Modern Medicine

基　　金：教育部博士点基金(No:20060660001);贵州省省长基金(No:2005-303)

摘　　要：目的动态观察糖尿病(DM)大鼠肾小管骨形态发生蛋白-7(BMP-7)和p38丝裂原活化蛋白激酶(p38MAPK)在糖尿病肾病(DN)发病机制中的相互关系。方法将SD大鼠分为正常对照组(N组)、糖尿病组(DM组)和糖尿病胰岛素治疗组(DMT组),分别于成模后2、4、8、12、16和24周测定生化指标和肾脏指数,PAS染色观察肾脏病理形态改变,免疫组织化学检测BMP-7、p-p38MAPK、α-SMA和FN蛋白的表达;RT-PCR方法检测肾皮质BMP-7mRNA的表达。结果随DM病程延长,BMP-7蛋白和mRNA的表达较N组低,至24周时BMP-7蛋白仍有少量表达但mRNA无表达,DMT组表达显著增多;p-p38MAPK蛋白于N组无表达,DM组显著增多,8周时达高峰,DMT组则显著减少;α-SMA开始表达于DM16周组,而DMT组无表达。24周DM组和DMT组BMP-7蛋白表达与24h尿蛋白、肾脏指数、α-SMA、FN和p-p38MAPK呈显著负相关。结论BMP-7与p38MAPK之间可能相互调节,共同参与糖尿病肾病的发生发展过程。[Objective] To observe the dynamic changes of bone morphogentic protein-7 （BMP-7） and p38MAPK in renal tubules of diabetic,and to explore their relationship. [Methods] Rats were randomly divided into normal control groups （group N）, diabetes meUitus groups （group DM） and diabetes mellitus insulin-treated groups （group DMT）. Biochemical parameters and kidney index were analysed at week 2, week 4, week 8, weekl2, week 16 and week 24. The changes of pathomorphology were examined in PAS staining section. Immunohistochemistry was employed to detect the expression of BMP-7, p-p38MAPK, α-SMA and FN protein in renal tubules of all groups. The mRNA level of BMP-7 in renal cortex was examined by RT-PCR. [ Results ] With development of diabetes melli- tus, the expression of BMP-7 protein and mRNA expression was gradually cut down, BMP-7 protein have a small expression, but mRNA lost in DM rats at week 24. Contrarily, the expression of BMP-7 protein and mRNA were upregulated remarkably in DMT rats as compared with those at synchronization of DM rats. Positive staining of p- p38MAPK was observed in DM rats by immunohistoehemistry, p-p38MAPK could be observed in DM rats at week 2 and reaehed the peak at week 8, which were down-regulated significantly in DMT rats （P 〈0.05）. In DM rats, tubular α-SMA staining was seen from week 16, but lost in DMT rats. In DM and DMT rats week 24, eorrelations were strongly negative among BMP-7 protein with urine protein, kidney index, α-SMA, FN and p-p38MAPK. [ Conclusion] There may be a regular relationship between BMP-7 and p38MAPK, whieh participates in the onset and pro-gression of diabetic nephropathy.

关 键 词：骨形态发生蛋白一7 P38丝裂原活化蛋白激酶 α一平滑肌肌动蛋白 糖尿病肾病 纤维连接蛋白 

分 类 号：R363[医药卫生—病理学] R-332[医药卫生—基础医学]