肾小管脂毒性在糖尿病肾病发病机制中的研究进展

Research progress of renal tubular lipotoxicity in the pathogenesis of diabetic nephropathy

糖尿病肾病(diabetic nephropathy,DN)是糖尿病的重要并发症,是终末期肾病的重要病因。DN患者常伴脂质代谢紊乱。脂代谢紊乱可致肾小管内脂质分布异常,引起肾脏脂肪堆积、脂滴积累、肾小管损伤等一系列“脂毒性”现象,进而诱发DN肾脏炎症、纤维化等病理改变。作为肾脏中的高耗能结构,肾小管脂代谢产能对维持其正常生理功能具有重大意义。脂质能量代谢在DN发病机制中发挥不可或缺的作用,本文从胆固醇代谢引起DN肾小管脂毒性、脂肪酸代谢引起DN肾小管脂毒性、脂代谢异常在肾小管与肾小球间的“串扰”作用以及肾小管脂毒性靶向药物治疗等方面进行阐述,旨在为今后临床防治DN新角度与新方案的提出提供参考。

Diabetic nephropathy(DN)is an important complication of diabetes mellitus and an important cause of end-stage renal disease.Patients with DN often have disorders of lipid metabolism.Disorders of lipid metabolism can lead to abnormal distribution of lipids in renal tubules,causing a series of“lipotoxic”phenomena such as renal fat accumulation,lipid droplet accumulation and tubular damage,which in turn induce DN kidney inflammation,fibrosis and other pathological changes.As a high energy-consuming structure in the kidney,lipid metabolic capacity is of great importance to maintain its normal physiological function.The role of lipid energy metabolism on DN and its mechanism of action are described in this paper from cholesterol metabolism-induced DN tubular lipotoxicity,fatty acid metabolism-induced DN tubular lipotoxicity,the role of abnormal lipid metabolism in the“crosstalk”between tubules and glomeruli,and the targeted drug therapy for tubular lipotoxicity,aiming to provide a reference for the new angle and new scheme of clinical prevention and treatment of DN in the future.