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骨形态发生蛋白--7及抑制性Smads在糖尿病肾病发生发展中的表达变化

杨勤, 韩冰, 谢汝佳, 程明亮

贵阳医学院病理生理学教研室.贵州,贵阳 550004

摘要

该文采用免疫组化、Western blot及荧光实时定量PCR方法,动态观察链脲佐菌素(streptozocin,STz)诱导的大鼠糖尿病肾病(diabetic nephropathy,DN)发生早期肾脏骨形态发生蛋白--7(bone morphogenetic protein--7,BMP--7)、Smad6、Smad7蛋白及mRNA表达。结果显示,在正常及DN大鼠肾小管均有BMP--7、Smad6、Smad7蛋白表达,以胞浆表达为主。DN大鼠BMP--7、Smad6蛋白表达较正常大鼠明显增多({sl P}＜0.05),且BMP--7的mRNA表达呈先增加后降低的状态;而Smad7蛋白和mRNA的表达均呈先增加后降低的状态。转化生长因子--#beta#1 (transforming growth factor--#beta#1,TGF--#beta#1)及Ⅰ型胶原(collagentype Ⅰ,COL--I)mRNA在DN大鼠肾脏表达较正常大鼠明显增多({sl P}＜0.05),且随着糖尿病进展有逐渐增加的趋势。结果提示,作为TGF--#beta#超家族信号分子的一员,BMP--7信号及抑制性Smad通路在DN肾纤维化发生早期可能起重要的反馈性抑制作用。

关键词： 糖尿病肾病; 骨形态发生蛋白-7; Smad6; Smad7; 转化生长因子-#beta#; 链脲佐菌素

Changes of bone morphogenetic protein--7 and inhibitory Smad expression in streptozotocin--induced diabetic nephropathy rat kidney

Yang Qin, Han Bing, Xie Rujia, Cheng Mingliang

Department of Pathophysiology, Guiyang medical university.Guiyang 550004,Guizhou

Abstract

The present study was designed to observe the expressions of bone morphogenetic protein-7 (BMP-7) and inhibitory Smads in kidney of rats with diabetic nephropathy (DN), and explore the possible mechanism of DN. Male Wistar rats weighing 180-220 g were single injected with streptozocin (STZ, 55 mg/kg body weight) for 2, 4, 8 and 16 weeks to induce DN. Blood glucose, kidney weight/body weight and 24-hour urine protein in the control and DN rats were examined; the expressions of BMP-7, Smad6 and Smad7 were detected by using immunohistochemical techniques, western blot and real-time PCR. The results showed that blood glucose and 24-hour urine protein in DN rats were higher than that in the control rats and kidney weight/body weight was also elevated in DN rats, especially in 16-week STZ-induced rats. The expressions of BMP-7 and Smad6 proteins in DN rats were elevated, while BMP-7 mRNA expression was increased 2 weeks after STZ injection and decreased 16 weeks after STZ injection. The expressions of Smad7 protein and mRNA were elevated in DN rats 2 weeks after STZ injection and decreased 16 weeks after STZ injection. In addition, the expression of transforming growth factor-#beta#1(TGF-#beta#1) and collagen type I(COL-I) mRNA were increased in DN rats. These results suggested in the early stage of DN, increase in BMP-7 and inhibitory Smads expression may play a role in the feedback regulation and restrain the development of DN.

Key words: diabetic nephropathy;bone morphogenetic protein-7;Smad6;Smad7;transforming growth factor-#beta#;streptozotocin

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引用本文：

杨勤, 韩冰, 谢汝佳, 程明亮. 骨形态发生蛋白--7及抑制性Smads在糖尿病肾病发生发展中的表达变化[J]. 生理学报 2007; 59 (2): 190-196.

Yang Qin, Han Bing, Xie Rujia, Cheng Mingliang. Changes of bone morphogenetic protein--7 and inhibitory Smad expression in streptozotocin--induced diabetic nephropathy rat kidney. Acta Physiol Sin 2007; 59 (2): 190-196 (in Chinese with English abstract).