脂质累积引起的肾小管间质损伤是慢性肾脏疾病进展的重要因素。CD36过表达引起肾小管间质摄取过多游离脂肪酸和氧化修饰低密度脂蛋白，继而诱导炎症和抑制脂肪酸氧化并导致了肾小管间质纤维化发生发展。本课题组观察到糖尿病肾病小鼠肾组织多聚体形式CD36表达上调，过表达的多聚体CD36与脂质配体具有共定位现象，提示病理状态的脂质摄取可能与CD36多聚体形成相关；此外，还观察到糖基化抑制会减少多聚体形成。因此，我们假设翻译后修饰影响CD36多聚体的形成，多聚体形成会促进脂质累积，并激活炎症信号和抑制脂肪酸氧化并促使肾纤维化发生。本项目拟探索CD36形成多聚体的结构基础，采用抑制剂和修饰位点突变的方法观察翻译后修饰对多聚体形成的影响，并在细胞系和小鼠体内观察多聚体形成是否影响脂质摄取、脂肪酸氧化、炎症诱导及纤维化进展。本项目将揭示CD36多聚体的作用和调控机制，为防治脂质肾损伤提供新的可能靶点。

Lipids accumulation induced tubulointerstitial injury is an important factor for progression of chronic kidney disease. Renal tubular epithelial cells and interstitial uptake excess free fatty acid and oxidative low density lipoprotein induced by overexpression of Type B of scavenger receptor CD36 caused renal lipid accumulation and promoted the development of renal tubular interstitial fibrosis by induce inflammation and impaired fatty acids oxidation. Our previous studies have found that palmitic acid would upregulated CD36 multimer expression in kidney of diabetic nephropathy mice，and also observed co-localization between CD36 multimer and lipids. Thus, lipids uptake on pathology condition may be associated with CD36 multimer formation. Moreover, our experiment results show that the inhibition of glycosylation can reduce the expression of CD36 multimer. We assume that the glycosylation modification can regulate the formation of CD36 multimer and lipids accumulation, and activate inflammatory signals and suppress fatty acids oxidation to promote renal fibrosis. This project is proposed to identify gathered form of CD36, explore glycosylation and others modification effect on the formation of multimer, and observe whether multimer formation affect the function of the lipids uptake, fatty acids oxidation and inflammation in tubulointerstitial lesions. This project will reveal mechanism of CD36 mutimer formation and regulation, and provide new possibility target for prevention and treatment of renal lipid injury.