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中华肾病研究电子杂志 ›› 2021, Vol. 10 ›› Issue (06) : 347 -351. doi: 10.3877/cma.j.issn.2095-3216.2021.06.010

综述

自噬在糖尿病肾病发病及治疗中的作用与机理
王书缘1, 袁震1, 王德坤1,(), 谭小月1,()   
  1. 1. 300071 天津,南开大学医学院
  • 收稿日期:2021-08-13 出版日期:2021-12-28
  • 通信作者: 王德坤, 谭小月
  • 基金资助:
    国家自然科学基金资助项目(81872254); 国家自然科学基金青年科学基金资助项目(82000708); 国家级大学生创新训练计划资助课题(201910055106)

Role and mechanism of autophagy in the pathogenesis and treatment of diabetic nephropathy

Shuyuan Wang1, Zhen Yuan1, Dekun Wang1,(), Xiaoyue Tan1,()   

  1. 1. Nankai University School of Medicine, Tianjin 300071, China
  • Received:2021-08-13 Published:2021-12-28
  • Corresponding author: Dekun Wang, Xiaoyue Tan
引用本文:

王书缘, 袁震, 王德坤, 谭小月. 自噬在糖尿病肾病发病及治疗中的作用与机理[J]. 中华肾病研究电子杂志, 2021, 10(06): 347-351.

Shuyuan Wang, Zhen Yuan, Dekun Wang, Xiaoyue Tan. Role and mechanism of autophagy in the pathogenesis and treatment of diabetic nephropathy[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2021, 10(06): 347-351.

自噬作为高度保守的溶酶体降解途径,通过降解细胞内蛋白质和细胞器,实现对胞内异常成分的清除及再利用。基础自噬为维持肾脏稳态所必需,而应激条件下诱导的自噬广泛参与到各类型肾脏细胞的适应性反应中。雷帕霉素哺乳动物靶蛋白(mTOR)、AMP激活的蛋白激酶(AMPK)以及沉默信息调节因子1(SIRT1)等营养感受信号通路,以及氧化应激、内质网应激、缺氧应激等细胞内应激信号通路共同调控糖尿病肾病条件下自噬的发生及进程。研究表明,自噬在糖尿病肾病中受到阻滞,而包括传统中草药在内的自噬激活药物显示出良好的应用前景。本文围绕糖尿病肾病条件下肾脏固有细胞自噬调控信号通路的最新研究进展进行综述,尤其关注自噬在中药及其有效成分治疗糖尿病肾病中的作用与机理。

As a highly conservative lysosomal degradation pathway, autophagy degrades intracellular proteins and organelles to achieve the elimination and reuse of intracellular abnormal components. Base-line autophagy is necessary to maintain kidney homeostasis, while stress-induced autophagy widely contributes to the adaptive responses of renal cells. Mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), silent information regulator 1 (SIRT1), and other nutrient-sensing signalling pathways, as well as intracellular stress signaling pathways such as oxidative stress, endoplasmic reticulum stress, and hypoxia stress, jointly regulate the onset and progression of autophagy under the condition of diabetic nephropathy. Studies have shown that autophagy was blocked in diabetic nephropathy, while autophagy-activating drugs including traditional Chinese herbal medicines showed good application prospects. This article summarized the latest research progress on the autophagy regulation signal pathways of kidney intrinsic cells under the condition of diabetic nephropathy, especially focusing on the role and mechanism of autophagy in the treatment of diabetic nephropathy with traditional Chinese medicine and its active ingredients.

图1 糖尿病肾病条件下参与自噬调控的信号通路注:mTORC1:哺乳动物雷帕霉素靶蛋白复合物1;AMPK:AMP依赖的蛋白激酶;SIRT-1:沉默信号调节因子1;TFEB:transcription factor EB,转录因子EB;ATG:自噬相关基因;FIP200: FAK family kinase-interacting protein of 200 kDa,与FAK家族激酶作用的分子量200 kD蛋白;VPS15:vacuolar protein sorting 15,液泡蛋白分选15;ATG14L:ATG14样蛋白;FOXO3a:forkhead box transcription factor O3a,叉头框转录因子O3a;BNIP3: BCL2/adenovirus E1B 19 kDa protein-interacting proteins 3,Bcl2/腺病毒E1B19kDa蛋白相互作用蛋白3;LC3:microtubule-associated protein 1 light chain 3,微管相关蛋白1轻链3;HIF-1α:hypoxia-inducible factor-1α,低氧诱导因子1α;eIF2α:eukaryotic initiation factor 2α,真核起始因子2α;PERK:protein kinase R-like endoplasmic reticulum kinase,蛋白激酶R样内质网激酶;ATF4: activating transcription factor 4,转录激活因子4;CHOP: CCAAT/enhancer-binding protein (C/EBP) homologous protein, CCAAT/增强子结合蛋白(C/EBP)同源蛋白质;ATF6: activating transcription factor 6,转录激活因子6;IRE1α:inositol-requiring protein 1α,需要肌醇蛋白1α
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