摘要
目的动态观察糖尿病大鼠肾小管转化生长因子-β1(TGF-β1)、丝裂原活化蛋白激酶(MAPK1/3)和纤维连接蛋白(FN)的变化,探讨其在肾小管间质病变发生发展中的作用。方法将大鼠分为正常对照组;糖尿病1周、2周、4周和8周组。用链脲菌素复制糖尿病模型;免疫组化法检测肾小管间质TGF-β1、MAPK1/3和FN的表达;Westernblot检测TGF-β1蛋白质;HE和PAS染色,光镜观察动物肾组织形态;生化法测定血糖、血肌酐及尿蛋白。结果正常肾小管可见少量MAPK1/3表达,而未见TGF-β1表达。糖尿病1周可见肾小管上皮细胞表达TGF-β1,并且随着病程发展而增加。MAPK1/3和FN从糖尿病两周开始表达亦呈持续增加,并且与TGF-β1及肾重/体重比呈正相关。糖尿病1周时MAPK1/3与TGF-β1无显著相关,但与FN呈正相关。结论大鼠糖尿病状态诱导肾小管表达TGF-β1并激活MAPK1/3,MAPK1/3介导高糖和TGF-β1的信号而促进FN的生成和沉积,在糖尿病肾脏肥大和纤维化中可能起重要作用。
AIM: To observe the expression of transforming growth factor β 1 (TGF-β 1), MAPK 1/3 and fibronectin (FN) in the development of renal tubulointerstitial disease. METHODS: Wistar male rats were randomly divided into normal control group, diabetic group of 1week, 2 weeks, 4 weeks and 8 weeks. Diabetic model was induced by peritoneal injection of streptozotocin. Immunohistochemistry was employed to detect the expression of TGF-β 1, MAPK 1/3 and FN in the kidney. TGF-β 1 protein in the renal cortex was checked by Western blot. BG, Scr and UP were analysed by biochemical methods, and the morphological changes in renal tubulointerstitium were also examined under microscopy on sections stained with HE and PAS. RESULTS: The expression of MAPK 1/3 and FN was observed, but not the expression of TGF-β 1 in normal renal tissue. Positive staining of TGF-β 1 was observed in the renal tubulo-interstitium in 1-week diabetic group and thereafter it increased in the course of diabetes. A continuous increase in the expression of MAPK 1/3 and FN was also observed in two - week diabetic rats. Chronologically the expression of TGF-β 1,MAPK 1/3 and FN and the ratio of KW/BW were positively correlative with each other in diabetic animals except one -week diabetic rats. There was also a positive correlation between MAPK 1/3 and FN in l -week diabetic rats. CONCLUSION: Our data suggest that TGF-β 1 appears in the renal tubulointerstitium in early period of diabetes and then its signal is mediated by MAPK 1/3 cascades to accelerate production of FN ,and in turn leads to renal hypertrophy and tubulointerstitial fibrosis. [
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2004年第9期1681-1685,共5页
Chinese Journal of Pathophysiology
基金
贵州省教育厅科学基金资助项目(No.2001036)
