脂代谢紊乱在肾脏衰老和肾纤维化中的作用  

Role of Lipid Metabolism Disorders in Renal Ageing and Renal Fibrosis

作　　者：吴胜泉 杨萌 刘新光 WU Sheng-Quan;YANG Meng;LIU Xin-Guang(Guangdong Provinvial Key Laboratory of Medical Molecular Diagnostics,Institute of Aging Research,Guangdong Medical University,Dongguan 523808,China;Institute of Biochemistry&Molecular Biology,Guangdong Medical University,Dongguan 523808,China)

机构地区：[1]广东医科大学衰老研究所,广东省医学分子诊断重点实验室,东莞523808 [2]广东医科大学生物化学与分子生物学研究所,东莞523808

出　　处：《生物化学与生物物理进展》2024年第5期1067-1078,共12页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(81971329,82200821);广东省基础与应用基础研究基金(2023A1515012838)资助项目。

摘　　要：肾间质纤维化是终末期肾脏病的病理基础,肾脏衰老是肾间质纤维化的危险因素。越来越多的研究证明,脂代谢紊乱会导致肾脏衰老和肾间质纤维化。脂代谢紊乱引起的脂质堆积,会造成脂毒性和细胞应激性损伤,从而诱发衰老与细胞外基质(extracellular matrix,ECM)的分泌。维持脂代谢稳态有助于减轻肾脏衰老与肾间质纤维化的发生发展。脂代谢途径的关键酶和调控蛋白有望成为改善肾脏衰老和肾间质纤维化的潜在靶点。本综述概括了脂代谢紊乱在肾脏衰老和间质纤维化中的作用,并对脂代谢中肾脏衰老和间质纤维化的预防靶点和策略进行了总结,为治疗肾纤维化发现新靶点提供了参考。Chronic kidney disease(CKD)has become a significant global public health problem.It is defined as chronic renal structural and functional dysfunction caused by various reasons.The prevalence of obesity and diabetes has increased dramatically in developing countries,which substantially affected the patterns of CKD observed in these regions.It’s inevitable that the disease spectrum of CKD is converting to metabolic diseases.CKD is also considered an independent risk factor for renal aging and cardiovascular disease in the elderly,which usually progresses to end-stage renal disease(ESRD).Renal interstitial fibrosis is the pathological basis of ESRD and is a microscopic manifestation of renal aging.Conversely,renal aging is a risk factor for interstitial fibrosis.Although the healthy kidney has a relatively low lipid level,CKD-associated dyslipidemia has been extensively studied.Nevertheless,less is known about the contribution of lipid disorders to the development of renal senescence and interstitial fibrosis.Recent studies have demonstrated that lipid metabolism disorders occur in the progress of renal aging and interstitial fibrosis.Renal lipids accumulate once lipid uptake and synthesis exceed the balance with lipolysis,which is mainly characterized by increased levels of triglyceride(TG)and oxidized lowdensity lipoprotein,and decreased levels of high-density lipoprotein.Excessive lipid accumulation in the kidney not only induces lipotoxicity and endoplasmic reticulum stress but also increases intracellular and mitochondrial reactive oxygen species,which induce stress injury and senescence in renal tubular epithelial cells.Proinflammatory and pro-fibrotic cytokines in a senescence-associated secretory phenotype secreted by senescent renal tubular epithelial cells further accelerate their senescence as well as the occurrence of inflammation and pericyte loss,promoting secretion of extracellular matrix(ECM)and subsequent fibrosis in the tubulointerstitial compartment.In addition,podocyte hypertrophy also leads to

关 键 词：肾脏衰老 肾间质纤维化 脂代谢 肾小管上皮细胞 

分 类 号：R365[医药卫生—病理学] R692[医药卫生—基础医学]