罗格列酮保护糖尿病肾病的作用机制研究

Mechanism of effect of rosiglitazone on diabetic nephropathy

目的研究罗格利酮作用于糖尿病肾病的作用机制。方法利用佐链脲菌素构建2型糖尿病肾病模型，在糖尿病模型成功后第4周开始分别用罗格列酮和雷帕霉素对模型大鼠进行干预；干预4、8周后处死大鼠，测空腹胰岛素、血脂、肾功能、尿微量白蛋白（Mau）；光镜显微镜观察肾小球形态；Wesgemblot方法观察肾脏LC3A／B及p—s6表达。结果成功地建立糖尿病大鼠模型；从动物外观、肾脏形态及肾功能观察罗格列酮和雷帕霉素对糖尿病肾病大鼠有一定保护作用，其中罗格列酮效果更佳；罗格列酮和雷帕霉素均可通过抑制mTOR信号通路，增强自噬活性，减轻糖尿病肾病损害。结论罗格列酮调控mTOR-自噬信号通路保护糖尿病肾病。

Objective To study the mechanism of the effect of rosiglitazone on diabetic nephropathy. Methods Type 2 diabetic nephropathy models were constructed with streptozocin. 4 weeks alter the construction, the model rats were intervened with rosiglitazone and rapamycin. 4 and 8 weeks after the intervention, the rats were killed and their fasting insulin, blood lipid, renal function, urinary mieroalbuminuria （Mau） were detected. The glomerular morphology was observed with light microscope. Western blot method was used to observe the expressions of LC3A/B and p-S6. Results The diabetic rat models were established successfully. Judging from the animal appearance, kidney morphology, and kidney function, rosiglitazone and rapamyein had protective effect on diabetic nephropathy rats and the effect of rosiglitazone was better. Both rosiglitazone and rapamycin could inhibit mTOR signaling pathways and enhance autophagy activity and reduce the damage of diabetic nephropathy. Couelusions Rosiglitazone regulates mTOR-autophagy pathway to protect diabetic nephropathy.