尾加压素Ⅱ和转化生长因子β1在糖尿病大鼠肾脏的表达及其意义  

Expressions of urotensinⅡ and TGF-β1 in kidney of diabetic rats and their significances

作　　者：田琳[1] 李才[1] 赵岩[1] 陈素贤[1] 苗春生[1] 

机构地区：[1]吉林大学药学院实验药理与毒理学教研室,吉林长春130021

出　　处：《吉林大学学报（医学版）》2007年第4期607-611,F0002,共6页Journal of Jilin University：Medicine Edition

基　　金：国家自然科学基金资助课题(30570855)

摘　　要：目的:观察尾加压素Ⅱ(UⅡ)和转化生长因子β1(TGF-β1)蛋白在糖尿病大鼠肾小管上皮细胞和肾小球的动态表达规律及其在糖尿病肾病发病中的作用。方法:30只雄性Wistar大鼠随机分为对照组及糖尿病2、4、8和12周组。糖尿病大鼠模型用单次腹腔注射链脲菌素(55mg·kg-1)诱发。生化法测定血糖、血和尿肌酐、尿白蛋白和尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG)含量。免疫组织化学法检测肾脏UⅡ、TGF-β1、纤连蛋白(FN)和Ⅳ型胶原(ColⅣ)的表达。结果:糖尿病各组大鼠的生化指标均明显高于对照组(P<0.05)。糖尿病大鼠肾小管上皮细胞和肾小球可见UⅡ和TGF-β1阳性染色颗粒,对照组未见该阳性染色颗粒。与糖尿病2周时比较,糖尿病4、8和12周组UⅡ和TGF-β1表达(阳性染色肾小管数和细胞数)随着病程进展进行性增加(P<0.05),肾小管上皮细胞UⅡ的表达水平与尿NAG含量呈正相关(r=0.895,P<0.01)。糖尿病组大鼠肾小管上皮细胞UⅡ与TGF-β1的表达水平呈正相关(r=0.769,P<0.01)。糖尿病8和12周组大鼠肾脏FN和ColⅣ表达明显高于对照组(P<0.05)。结论:糖尿病大鼠肾小管上皮细胞和肾小球UⅡ及TGF-β1蛋白表达均明显增加,提示其在糖尿病肾病的肾小管损害及细胞外基质积聚中可能起一定作用。Objective To investigate the dynamic expressions of urotensinⅡ （U Ⅱ） and transforming growth factor-β1 （TGF-β1） in renal tubular epithelial cells and glomeruli of diabetic rats and their roles in pathogenesis of diabetic nephropathy （DN）. Methods Thirty male Wistar rats were randomly divided into normal control, 2-week （2-wk DM）, 4-week （4-wk DM）, 8-week （8-wk DM） and 12-week （12-wk DM） diabetic groups. Diabetic model was induced by a single intraperitoneal injection of streptozotocin （55 mg·kg^-1）. Blood glucose （BG）, serum and urinary creatinine, urinary albumin （UAlb） and urinary N-acetyl-B-D-glucosaminidase （NAG） contents were dertemined with biochemical methods. Immunohistochemistry was used to detect the expressions of U Ⅱ , TGF-β1, fibronectin （FN） and collageniv （Col Ⅳ） in the kidney. Results BG, creatinine clearance （Ccr）, UA1b and NAG levels were significantly elevated in diabetic groups （P〈0.05）. As compared with control, positive staining of U Ⅱ and TGF-β1 was observed in the renal tubular epithelial cells and glomeruli of diabetic rats. Progressively increased U Ⅱ and TGF-β1 expressions were found in 4-, 8- and 12-wk DM groups （P〈0.05） with diabetic course compared with 2-wk DM. The expression of U Ⅱ protein in the renal tubular epithelial cells was positively correlated with urinary NAG content （r=0. 895, P〈0.01）. The expression level of U Ⅱ in the renal tubular epithelial cells was positively correlated with that of TGF-β1 （r=0. 769, P〈0. 01）. The expressions of FN and Col Ⅳ in diabetic kidney in 8- and 12-wk DM groups were obviously increased compared with normal control （P〈0. 05）. Conclusion The expressions of UⅡ and TGF-β1 proteins are markedly increased in the renal tubular epithelial cells and glomeruli of diabetic rats, suggesting that U Ⅱ and TGF-β1 may play roles in the renal tubular lesion and extracellular matrix accumulation of diabetic nephropathy.

关 键 词：尾加压素Ⅱ 转化生长因子Β 糖尿病肾病 纤连蛋白类 胶原Ⅳ型 

分 类 号：R587.1[医药卫生—内分泌] R-332[医药卫生—内科学]