摘要
本文采用免疫组化、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(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-β1(transforming growth factor-β1,TGF-β1)及Ⅰ型胶原(collagen typeⅠ,COL-Ⅰ)mRNA在DN大鼠肾脏表达较正常大鼠明显增多(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-β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。
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 mR.NA 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-β1 （TGF-β1） 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.
出处
《生理学报》
CAS
CSCD
北大核心
2007年第2期190-196,共7页
Acta Physiologica Sinica
基金
This work was supported by Chun Hui International Cooperation Program of Ministry of Education and Advanced Level Talents Fund of Guizhou Province.
