肾脏疾病中线粒体脂代谢与脂毒性的研究进展  

Research progress on mitochondrial lipid metabolism and lipotoxicity in kidney diseases

作　　者：孙珺 郭兆安[2] SUN Jun;GUO Zhaoan(School of Traditional Chinese Medicine,Shandong University of Traditional Chinese Medicine,Ji'nan 250014,China;Department of Nephrology,Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Ji'nan 250014,China)

机构地区：[1]山东中医药大学中医学院,济南250014 [2]山东中医药大学附属医院肾内一科,济南250014

出　　处：《生命的化学》2023年第4期549-557,共9页Chemistry of Life

摘　　要：作为高能耗器官,肾脏依赖大量的线粒体氧化脂肪酸提供能量。肾脏病理状态下白细胞分化抗原36(cluster of differentiation 36,CD36)、过氧化物酶体增殖物激活受体(peroxisome proliferator activated receptor,PPARs)、AMP依赖蛋白激酶(adenosine 5'-monophosphate-activated protein kinase,AMPK)和过氧化物酶体增殖激活受体γ辅助激活因子1α(peroxisome proliferator activated receptor gamma coactivator-1α,PGC-1α)等多种调节蛋白异常表达参与脂肪酸氧化缺陷,引发线粒体脂代谢紊乱和异位脂质堆积。异位脂质通过促炎、促凋亡和氧化应激等方式对肾脏及线粒体自身结构造成损伤,并且与血脂相互影响。线粒体脂肪酸氧化激动剂、心磷脂靶向肽和抗氧化剂以恢复线粒体稳态和功能为前提,保护肾脏免受脂毒性损伤,帮助肾功能的恢复。了解肾脏线粒体脂代谢的调控机制,进一步研发更为精准、高效的线粒体脂代谢调节剂,有望成为治疗用药的新方向。As a high energy consumption organ,kidney relies on a large number of mitochondrial oxidized fatty acids to provide energy.Abnormal expression of various regulatory proteins such as cluster of differentiation 36,peroxisome proliferator activated receptor,adenosine 5'-monophosphate-activated protein kinase,and peroxisome proliferator activated receptor gamma coactivator-lαin renal pathological conditions is involved in fatty acid oxidation defects,leading to mitochondrial lipid metabolism disorders and ectopic lipid accumulation.Ectopic lipids cause damage to the kidney and mitochondrial structure through pro-inflammatory,pro-apoptotic and oxidative stress,and interact with blood lipids.Mitochondrial fatty acid oxidation agonists,cardiolipin-targeting peptides,and antioxidants target mitochondrial homeostasis and function,protect the kidney from lipotoxic injury,and contribute to the recovery of renal function.Understanding the regulatory mechanism of renal mitochondrial lipid metabolism and further developing more precise and efficient mitochondrial lipid metabolism regulators to prevent renal lipotoxic damage by targeting mitochondria are expected to become a new direction for therapeutic drugs.

关 键 词：线粒体 脂肪酸 脂代谢 脂毒性 

分 类 号：R692[医药卫生—泌尿科学]