基于足细胞自噬探讨芒果苷防治糖尿病肾病的分子作用机制

肾脏足细胞受损是糖尿病肾病(DN)发生发展的关键病理生理过程，保护足细胞是目前寻找防治DN创新药物的研究热点。新近研究发现，自噬对于维持足细胞的正常结构和功能是必不可少的。因此有效干预足细胞自噬，将有利于防治DN。前期研究表明源于芒果叶的一种天然产物芒果苷具有较好的降糖活性，对糖尿病肾脏有一定的保护作用，但机制不明。据此，本研究将在前期研究基础上采用链脲霉素诱导形成DN大鼠，深入研究芒果苷对DN足细胞的保护作用，并采用基因转染、实时荧光定量PCR、Western Blot和电镜等技术在细胞和分子水平研究芒果苷对足细胞自噬通路及其上游调控信号通路关键靶点AMPK、mTOR 、LC3等的干预作用，探讨其作用机制，为芒果苷的深入研究和开发提供理论和实验依据，也为DN的防治策略提供新的理论依据。

Podocyte impairment is one of key pathophysiological processes during the occurrence and development of diabetic nephropathy (DN). It has currently been highlighted to screening for new drugs to treat DN based on the protection of podocyte. Recent reports found that autophagy might be essential to maintain the homeostasis and functions of podocytes, which might be altered in diabetic condition. Therefore the effective intervention of podocyte autophagy would be benificial to the prevention and treatment strategy for DN. Previous studies showed that mangiferin, a natural product from Mangifera indica L., has potential hypoglycemic activity and protective effect on kidney in diabetic animals. However, the protective effect mechanism of mangiferin remains unclear. Therefore, in the present study, the renoprotective effects of mangiferin, especially on podocytes, will be investigated in diabetic rats induced by streptozocin. Its molecular mechanisms underlying the autophagy pathway and upstream regulatory pathways will be investigated at the cellular and molecular level. The implementation of the investigation will offer the theoretical and experimental evidences for the application of mangiferin to treat DN.