脂质代谢紊乱是肾脏疾病进展的独立危险因素，研究脂质肾损伤的发生机制及防治措施对延缓慢性肾脏病进展具有重要意义。高脂血症时肾脏系膜细胞能通过自身SCAP-SREBP-2-LDLr负反馈调节减少肾脏对脂质摄取，从而防止泡沫细胞形成所导致的肾脏纤维化。ACE2-Ang(1-7)-Mas轴参与抗增生、抗炎、抗纤维化以及机体物质能量代谢，但在脂质肾损伤中的研究国内外尚无报道。本项目旨在前期工作基础上首次探讨在高脂培养的系膜细胞及C57BL/6小鼠脂质肾损伤模型中，ACE2-Ang(1-7)-Mas轴通过增强SCAP-SREBP-2-LDLr负反馈调节降低LDLr表达、改善脂质代谢；进而通过抑制纤维生成及降解信号通路TGF-β/Smad3-CTGF、TGF-β/Smad3-TIMPs/PAI，抑制脂质导致的肾脏纤维化，以明确该轴在改善脂质代谢及脂质肾损伤的机制及地位，为临床治疗慢性肾脏病提供理论依据。

Lipid metabolic disorder is an independent risk factor for the development of renal disease. Researching the mechanism of lipid-induced renal injury and exploring its effective prevention and control measures are extraordinary significant to slow the progression of chronic kidney disease. In the hyperlipidemic state, mesangial cells can maintain steady cholesterol levels via negative feedback of SCAP-SREBP-2-LDLr, which alters receptor expression, to avoid excessive lipid accumulation and prevent renal fibrosis caused by the formation of foam cells. The ACE2-Ang(1-7)-Mas axis opposes proliferation, inflammation, oxidative stress，profibrotic actions, and participates in energy metabolism. However, the role of this axis in lipid-induced renal injury is unclear at present. Based on our previous work, this project aims to first show that the expression of the ACE2-Ang(1-7)-Mas axis in high-fat cultured mesangial cells and in a lipid-induced renal injury model in C57BL/6 mice can reduce the expression of LDLr to reduce lipid deposition in the kidney by enhancing SCAP-SREBP-2-LDLr negative feedback, adjust the fibrotic matrix-generated signal transduction pathway TGF-β/Smad3-CTGF, fiber substrate biodegradation signaling pathway TGF-β/Smad3-TIMPs/PAI,furthermore, to play an important role in reducing fibrosis formation in lipid-induced renal injury. Through this project, we can elucidate the mechanism and position of the ACE2-Ang(1-7)-Mas axis on improving both lipid metabolism and lipid-induced renal injury, and provide a new theoretical basis and new ideas for the clinical treatment of lipid-induced renal injury.