mTOR-自噬信号通路在大鼠糖尿病肾病中的作用研究

The role of mTOR - autophagy signaling pathway in diabetic nephropathy of rats

目的研究mTOR-自噬信号通路在糖尿病肾脏损害中的作用。方法将SD大鼠分为正常组和对照组，对照组利用佐链脲菌素构建2型糖尿病肾病模型，8周后检测两组大鼠的体重、肾重、血生化指标、尿微量白蛋白；光镜显微镜观察肾小球、肾小管形态；Western blot方法观察肾脏P—S6及LC3A／B表达。结果成功地建立糖尿病大鼠模型，发现对照组大鼠体重减少，肾重增加，血糖、甘油三酯及尿素氮升高，而胆固醇及白蛋白有下降，尿微量白蛋白增加；光镜可见对照组大鼠。肾小球肥大，系膜膜细胞增生、系膜基质增多；Western blot发现对照组大鼠。肾组织的自噬活性明显降低，表现为LC3A／B降低；mTOR被激活，表现P—s6水平升高。结论糖尿病肾病中mTOR活化，自噬能力下降，mTOR-自噬信号通路可能是糖尿病肾病的发病机制之一。

Objective To study the role ofmTOR - autophagy signaling pathway in diabetic nephropathy of rats. Methods The SD rats were divided into the normal group and the control group, and the control group was constructed type 2 diabetic nephropathy model with streptozocin. 8 weeks later, we tested body weight, kidney weight, urine trace albumin, blood biochemical item of the rats. Glomerulus and renal tubule were observed by light microscopy. The renal LC3A/B and p-S6 expression were tested by Western blot. Results Diabetic rats model was established successfully. We found weight loss, kidney weight increase, blood sugar, triglyceride, and urea nitrogen increased, but the cholesterol and albumin decreased, urine trace albumin increased in the control group; the glomerulus hypertrophied, mesangial membrane cell proliferation and mesangial matrix increased; Western blot found that kidney tissues autophagy activity of diabetic rats significantly decreased as the LC3A/B decreased; mTOR was activated, because the p-S6 level increased. Conclusions roTOR activation and autophagy ability decline are found in the diabetic nephropathy, mTOR - autophagy signaling pathway may be one of the pathogenesis of diabetic nephropathy.