肾脏肥大是早期糖尿病肾病主要病理特征。哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）活化促进蛋白合成，刺激细胞增殖肥大，调控并耦联线粒体生物合成增加为细胞增殖肥大提供能量。中药单体黄芪甲苷可抑制mTOR活化并调控线粒体生物合成。本项目基于课题组前期工作：黄芪甲苷减小糖尿病小鼠肾小球和肾小管的肥大，糖尿病肾组织细胞存在mTOR活化和线粒体数量增加；拟采用mTOR特异性抑制剂雷帕霉素下调mTOR蛋白表达，并应用黄芪甲苷进行干预，通过体内外观察糖尿病状态下肾组织细胞mTOR对线粒体生物合成的调控作用以及黄芪甲苷的干预靶点。旨在明确mTOR和线粒体生物合成在糖尿病肾脏肥大中的作用，及黄芪甲苷糖尿病肾脏保护作用是否依赖其对mTOR和其调控线粒体生物合成的抑制效应。本课题意义在于为糖尿病肾病的中药防治提供新靶点，并阐明黄芪甲苷糖尿病肾病保护的分子机制。

Renal hypertrophy is the major pathological feature in the earlier stage of diabetic nephropathy. The mammalian target of rapamycin (mTOR) stimulates protein synthesis and drive cell growth and proliferation. mTOR also regulates and coordinates mitochondrial biogenesis, which provides energy for cell growth and proliferation. Astragaloside Ⅳ, a Chinese herb monomer, inhibits mTOR activity and regulates mitochondrial biogenesis. Our previous results demonstrated that mTOR was activated and the number of mitochondrial was increased in diabetic kidney. Astragaloside Ⅳ reduced the increased glomerular and tubular size in experimental diabetes. In order to investigate the effect of mTOR on mitochondrial biogenesis and the possible treatment target of astragaloside Ⅳ to diabetic renal cells, rapamycin, a specific inhibitor for mTOR, will be used to down-regulate the mTOR protein level in renal cells under diabetic conditions in this experiment. The aim of this study is not only to clarify the role of mTOR and mitochondrial biogenesis in diabetic renal hypertrophy, but also to define whether the diabetic renal protective effect of astragaloside Ⅳ is dependent on its inhibition of the mTOR and mitochondrial biogenesis. The significance of this project is to provide new Chinese medicine prevention and treatment targets for diabetic nephropathy,and to clarify the molecular mechanisms that astragaloside Ⅳ protect the diabetic kidney.