Yang Qin, Han Bing, Xie Ru-Jia, Cheng Ming-Liang
Department of Pathophysiology, Guiyang Medical College, Guiyang, China.
Sheng Li Xue Bao. 2007 Apr 25;59(2):190-6.
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 expressions of transforming growth factor-beta1 (TGF-beta1) and collagen type I (COL-I) mRNA were increased in DN rats. These results suggest in the early stage of DN, increase in BMP-7 and inhibitory Smad expression may play a role in the feedback regulation and restrain the development of DN.
本研究旨在观察糖尿病肾病(DN)大鼠肾脏中骨形态发生蛋白-7(BMP-7)和抑制性Smads的表达,并探讨DN的可能机制。选取体重180 - 220 g的雄性Wistar大鼠,单次注射链脲佐菌素(STZ,55 mg/kg体重),分别诱导2、4、8和16周以建立DN模型。检测对照组和DN大鼠的血糖、肾重/体重及24小时尿蛋白;采用免疫组化技术、蛋白质印迹法和实时荧光定量PCR检测BMP-7、Smad6和Smad7的表达。结果显示,DN大鼠的血糖和24小时尿蛋白高于对照组大鼠,且DN大鼠的肾重/体重也升高,尤其是在STZ诱导16周的大鼠中。DN大鼠中BMP-7和Smad6蛋白表达升高,而BMP-7 mRNA表达在STZ注射后2周增加,在STZ注射后16周降低。Smad7蛋白和mRNA表达在STZ注射后2周升高,在STZ注射后16周降低。此外,DN大鼠中转化生长因子-β1(TGF-β1)和I型胶原(COL-I)mRNA表达增加。这些结果提示,在DN早期,BMP-7和抑制性Smad表达增加可能在反馈调节中起作用,并抑制DN的发展。