足细胞损伤机制及其治疗糖尿病肾病潜在策略的研究进展

doi:10.13481/j.1671-587X.20250531

摘要/Abstract

摘要：

糖尿病肾病（DN）是全球范围内终末期肾病的主要致病因素，其发病机制涉及多重细胞和激素分子通路失调。足细胞在DN进程中发挥核心作用，其损伤程度与蛋白尿、肾小球滤过率和肾小球硬化等肾脏损伤的病理变化有密切关联。然而，由于氧化应激、脂质代谢异常和线粒体损伤等多种机制复杂且相互影响，足细胞损伤的确切机制尚待阐明。现结合国内外关于DN足细胞损伤核心机制的研究进展，并归纳总结针对上述机制在DN治疗中的研究和应用，特别是其所衍生的潜在治疗靶点及相关药物研发动态，为开发DN临床治疗策略提供理论依据。

关键词: 足细胞, 损伤机制, 糖尿病肾病, 治疗靶点, 肾素-血管紧张素-醛固酮系统, 线粒体损伤

Abstract:

Diabetic nephropathy （DN） is a significant causative factor of end-stage renal disease globally， and its pathogenesis involves dysregulation of multiple cellular and hormonal pathways. Podocytes play crucial roles in the process of DN， with the extent of podocyte injury closely associated with key pathological manifestations of renal damage， such as proteinuria， glomerular filtration rate， and glomerulosclerosis. However， due to the complexity and interplay of mechanisms contributing to podocyte injury， such as oxidative stress， abnormal lipid metabolism， and mitochondrial damage， the precise mechanisms underlying podocyte injury remain incompletely understood. This review integrated the latest research findings from both domestic and international studies on the core mechanisms of podocyte injury in DN. Furthermore， this article summarized the implications of these mechanisms for DN treatment， particularly focusing on potential therapeutic targets and the development of related pharmacological interventions derived from targeting podocyte injury pathways， so as to provide a theoretical foundation for the development of clinical therapeutic strategies for DN.

Key words: Podocyte, Injury mechanism, Diabetic nephropathy, Therapeutic target, Renin-angiotensin-aldosterone system, Mitochondrial damage

中图分类号:

R329.2

卢洵,马程忻,杨佳楠,郭欣欣,谢晓蓓,赵冰海,李洪志. 足细胞损伤机制及其治疗糖尿病肾病潜在策略的研究进展[J]. 吉林大学学报(医学版), 2025, 51(5): 1415-1422.

Xun LU,Chengxin MA,Jianan YANG,Xinxin GUO,Xiaobei XIE,Binghai ZHAO,Hongzhi LI. Research progress in mechanism of podocyte injury and its potential therapeutic strategies for diabetic nephropathy[J]. Journal of Jilin University(Medicine Edition), 2025, 51(5): 1415-1422.

图/表 1

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Target site	Expression	Pathway	Mechanism	Reference
Klotho	↑	Nrf2/ARE	Anti-oxidation，anti-apoptosis	[21]
USP15	↓	Nrf2/ARE	Anti-oxidation，anti-inflammatory	[22]
GSK-3β	↓	Nrf2/ARE	Anti-oxidation	[23]
TRIM32	↓	AKT/GSK-3β/Nrf2	Anti-oxidation，anti-apoptosis	[24]
REDD1	↓	AKT/GSK-3β/Nrf2	Anti-oxidation，anti-apoptosis	[25]
LncRNA 1500026H17Rik	↓	miR-205-5p/EGR1	Anti-oxidation,anti-fibrosis,anti-inflammation	[26]
LncRNA SNHG5	↓	miR-26a-5p/TRPC6	Anti-oxidation，anti-apoptosis	[27]
FOXO3a	↓	AOPPs/ROS/mTOR	Anti-oxidation，anti-apoptosis	[28]
Rab11	↓	Ang Ⅱ/Rab11/LDLR	Reduce lipid accumulation	[32]
JAML	↓	SIRT1-AMPK/SREBP1	Reduce lipid accumulation	[10]
GPR43	↓	ERK/EGFR1	Reduce lipid accumulation	[33]
STING	↓	mtDNA-cGAS-STING	Reduce lipid accumulation	[34]
CCDC 92	↓	ABCA1	Reduce lipid accumulation	[35]
CD36	↓	CD36/ROS/TRPC6	Anti-oxidation, reduce lipid accumulation	[36]
GPD1	↓	Ang Ⅱ/DHAP/G-3-P	Reduce lipid accumulation	[39]
SIRT6	↑	Ang Ⅱ/ROCK1/DRP1	Reduce mitochondrial dynamic imbalance	[40]
SOCE	↓	Ang Ⅱ/IP₃， DAG/TRPC6	Alleviate mitochondrial respiratory dysfunction	[41]
LncRNA 585189	↓	hnRNA A1/SIRT1	Alleviate mitochondrial dysfunction	[42]
PKM2	↑	HIF-α/VEGF	Anti-oxidation, improve mitochondrial function	[43]
AKAP1-DRP1	↓	MAMs/AKAP1-DRP1	Inhibit excessive mitochondrial division	[44]
AT2R	↑	RAS/AT1R, NOS	Anti-apoptosis,anti-fibrosis,anti-inflammation	[47]
Ang Ⅱ	↓	PI3K/AKT/NF?κB	Anti-oxidation， anti-apoptosis	[48]