杨桃根DMDD调控内质网应激-自噬crosstalk减轻糖尿病肾病肾小管上皮细胞损伤的机制研究

内质网应激(ERS)与自噬之间交互效应，即Crosstalk，可协同调节细胞凋亡等生物学过程，在糖尿病肾病（DN）中具有重要作用。我们前期研究发现杨桃根DMDD能明显改善糖尿病所致肾损伤，并可抑制糖尿病小鼠肾组织及高糖诱导下肾小管上皮细胞（HK-2）中ERS标志蛋白CHOP、GRP78的表达，同时能下调自噬蛋白Beclin1、Atg5的表达。提示，DMDD对DN肾小管上皮细胞ERS和自噬的双重调控作用，可能与启动ERS-自噬Crosstalk有关，但机制尚未明确。本项目拟在前期研究的基础上，通过建立DN细胞及小鼠模型，探讨ERS与自噬介导DN肾小管上皮细胞损伤的机制，并从调控Ca2+途径、IRE1途径、PERK途径等信号通路角度分析DMDD启动ERS-自噬Crosstalk的机理，继而较全面地揭示其抗DN肾小管上皮细胞损伤的分子机制，为其治疗DN提供实验依据和理论支持。

The interaction effect between er stress (ERS) and autophagy, namely Crosstalk, can coordinate the regulation of cell apoptosis and other biological processes, which plays an important role in diabetic nephropathy (DN). Our previous study found that starfruit root DMDD could significantly improve the expression of kidney injury caused by diabetes, inhibit the expression of ERS marker proteins CHOP and GRP78 in renal tubular epithelial cells (hk-2) in diabetic mice and the expression of autophagic proteins Beclin1 and Atg5 in hk-2 cells. It is suggested that the dual regulatory effects of DMDD on ERS and autophagy of DN renal tubular epithelial cells may be related to the initiation of ers-autophagy Crosstalk, but the mechanism has not been fully identified. The project is proposed on the basis of previous studies, through the establishment of DN cells and mouse model, ERS and autophagy mediated DN, the mechanism of renal tubular epithelial cell damage and the control way of Ca2 +, IRE1 pathway, PERK ways such as Angle of signaling pathways DMDD adjust ERS - molecular mechanism of autophagy Crosstalk, which in turn reveals the overall resistance to DN molecular mechanism of renal tubular epithelial cell damage, provide the experimental basis and theoretical support for the treatment of DN.