[1]冯培东,张晓凤.NOD样受体家族含热蛋白结构域蛋白3炎性小体在糖尿病肾病纤维化中的致病环路：小分子抑制剂的靶向可行性与跨脏器炎症联动[J].陕西医学杂志,2026,(4):572-576，封三.[doi:DOI:10.3969/j.issn.1000-7377.2026.04.025]
　FENG Peidong,ZHANG Xiaofeng.Research progress of endocannabinoid system for renal fibrosis[J].,2026,(4):572-576，封三.[doi:DOI:10.3969/j.issn.1000-7377.2026.04.025]
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NOD样受体家族含热蛋白结构域蛋白3炎性小体在糖尿病肾病纤维化中的致病环路：小分子抑制剂的靶向可行性与跨脏器炎症联动

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2026年4期
页码:
572-576，封三
栏目:
综述
出版日期:
2026-04-05

文章信息/Info

Title:
Research progress of endocannabinoid system for renal fibrosis
作者:
冯培东1; 张晓凤2
（1.陕西中医药大学，陕西 咸阳712046；2.陕西省中医医院，陕西 西安710003）
Author(s):
FENG Peidong1; ZHANG Xiaofeng2
（1.Shaanxi University of Chinese Medicine,Xianyang 712046,China；2.Shaanxi Provincial Hospital of Traditional Chinese Medicine,Xi’an 710003,China）
关键词:
糖尿病肾病; NOD样受体家族含热蛋白结构域蛋白3; 肾纤维化; 细胞焦亡; 小分子抑制剂; 跨脏器炎症联动; 代谢应激
Keywords:
Diabetic nephropathy; NLRP3; Renal fibrosis; Pyroptosis; Small molecule inhibitors; Crossorgan inflammation linkage; Metabolic stress
分类号:
R 587.1
DOI:
DOI:10.3969/j.issn.1000-7377.2026.04.025
文献标志码:
A
摘要:
糖尿病肾病（DN）是全球终末期肾病（ESRD）的首要病因，其肾间质纤维化是决定肾功能不可逆下降的共同病理终点。作为先天免疫系统中最具“代谢感应”特征的炎症平台之一，NOD样受体家族含热蛋白结构域蛋白3（NLRP3）炎性小体通过感受高糖、脂毒、尿毒素、晶体与线粒体损伤等危险信号，引发白细胞介素-1β/白细胞介素-18（IL-1β/IL-18）成熟与GasderminD介导的细胞焦亡(Pyroptosis)，驱动肾小管间质炎症纤维化放大环路，并与转化生长因子-β(TGF-β)/Smad 信号通路、Wnt/β连环蛋白通路（Wnt）、肾素血管紧张素醛固酮系统（RAAS）、环鸟腺苷酸合成酶干扰素基因刺激因子通路等通路相互强化。近年出现的直接或功能选择性 NLRP3 抑制剂为“炎性小体纤维化”轴提供了可药性的干预切入点，但其疗效安全性窗口、组织渗透与面向肾脏疾病的临床证据仍待强化。DN 发生发展还体现为以 NLRP3/IL-1 轴为核心的跨脏器炎症联动（脂肪肝心肾视网膜肠道骨髓），提示“以肾为靶、系统校准”的联合策略更具现实可行性。本文综述 DN 中 NLRP3 的分子病理、细胞靶点与组织层级证据，评估小分子抑制剂的靶向前景并从“肾心肠骨髓轴”角度讨论系统性炎症的回路化特征与生物标志物体系。
Abstract:
Diabetic nephropathy （DN） represents the leading etiology of endstage kidney disease （ESKD） globally,with renal interstitial fibrosis constituting the common pathological endpoint that determines the irreversible deterioration of kidney function.As one of the most prominent “metabolic sensing” inflammatory platforms within the innate immune system,the NLRP3 inflammasome detects danger signals such as hyperglycemia,lipotoxicity,uremic toxins,crystals,and mitochondrial damage,thereby facilitating the maturation of IL-1β/IL-18 and Gasdermin Dmediated pyroptosis.This process drives the amplification loop of tubularinterstitial inflammationfibrosis and mutually reinforces interactions with pathways including TGF-β/Smad,Wnt,RAAS,and cGASSTING.In recent years,emerging direct or functionally selective NLRP3 inhibitors have provided druggable intervention points for the “inflammasomefibrosis” axis,although their efficacysafety window,tissue penetration,and clinical evidence tailored to kidney diseases require further substantiation.The pathogenesis and progression of DN also manifest as crossorgan inflammatory linkages centered on the NLRP3/IL-1 axis （encompassing adiposeliverheartkidneyretinaintestinebone marrow networks）,underscoring the practical feasibility of combined strategies that “target the kidney with systemic calibration”.This review synthesizes the molecular pathology,cellular targets,and tissuelevel evidence of NLRP3 in DN,evaluates the targeting prospects of smallmolecule inhibitors,and discusses the circuitous features of systemic inflammation along with biomarker frameworks from the perspective of the “kidneyheartintestinebone marrow axis” .

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备注/Memo

备注/Memo:
国家自然科学基金资助项目（81873201）
更新日期/Last Update: 2026-04-05