<i>NLRP3</i>炎性小体在狼疮性肾炎中的研究进展

闫德超; 王晓燕

doi:10.16766/j.cnki.issn.1674-4152.004305

NLRP3炎性小体在狼疮性肾炎中的研究进展

doi: 10.16766/j.cnki.issn.1674-4152.004305

闫德超^{1, 2},
王晓燕^{1, 2, ,}

1.
南京医科大学附属明基医院肾脏内科，江苏南京 210019
2.
南京医科大学附属明基医院中心实验室

基金项目:

国家自然科学基金项目 81970605

江苏省研究生科研与实践创新计划项目 SJCX24-0758

详细信息

通讯作者:
王晓燕，E-mail：xiaoyan51@hotmail.com

中图分类号: R593.242
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- 被引次数: 0
出版历程
- 收稿日期: 2025-03-25
- 网络出版日期: 2026-03-13

Research progress of NLRP3 inflammasome in lupus nephritis

YAN Dechao^{1, 2},
WANG Xiaoyan^{1, 2
, ,}

1.
Department of Nephrology, the Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, Jiangsu 210019, China

摘要

摘要: 作为系统性红斑狼疮(SLE)严重的临床并发症之一，狼疮性肾炎(LN)严重影响SLE患者的生活质量和疾病预后，增加慢性肾脏病的发病率和死亡率。作为NLR家族成员，NLRP3炎性小体是由ASC、NLRP3蛋白和pro-caspase-1组成的多蛋白复合体，可通过经典途径、非经典途径及替代途径等3种方式进行启动激活，其活化引发炎症细胞因子释放，进而损伤组织和细胞，在LN等多种自身免疫疾病的发病机制中扮演关键角色。NLRP3炎性小体在LN中可以累及多种肾脏细胞，尤其是肾脏足细胞和肾小管细胞，可以检测到荧光定位和蛋白表达显著增加。多种上游调节因子可通过活化NLRP3炎性小体及其相关成分启动炎症激活，进而加速LN疾病进展，包括GBP家族(GBP3、GBP5)、CD36、PIM1、IRF2、S1P等。此外，多项研究通过抑制NLRP3炎性小体活化，缓解和治疗LN，FGF21、SIRT1等内源性因子表达增加，或者外源性使用植物化学物质(和厚朴酚、表没食子儿茶素没食子酸酯、原花青素B2、淫羊藿苷、黄芩素、人参皂苷活性代谢产物M1、熊果酸、三七总皂苷及柠檬醛等)、NLRP3抑制剂MCC950、NF-κB抑制剂Bay11-7082、褪黑激素、氙气及三七注射液，调节NLRP3炎性小体表达来改善LN的病情和预后。本文系统总结NLRP3炎性小体的构成和激活机制及其在LN中的活化因素，并探讨靶向NLRP3炎性小体的LN治疗策略，特别强调了植物化学物质的潜在治疗效果，为LN相关药物和治疗方案的开发提供新的思路。
- 狼疮性肾炎 /
- 炎性小体 /
- 核苷酸结合寡聚结构域样受体蛋白3 /
- 植物化学物质
Abstract: Lupus nephritis (LN) is one of the most severe clinical complications of systemic lupus erythematosus (SLE), It significantly impairs the quality of life and prognosis of SLE patients, and is associated with a higher incidence of chronic kidney disease (CKD) and mortality in patients with CKD. The NLRP3 inflammasome is a multi-protein complex belonging to the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family. It consists of the following proteins: ASC, NLRP3, and pro-caspase-1. The inflammasome can be activated via three distinct pathways: the classical pathway, the non-classical pathway, and the alternative pathway. The process of activation has been demonstrated to initiate the release of pro-inflammatory cytokines, thus inducing tissue and cellular damage. It has been determined that this process plays a pivotal role in the pathogenesis of numerous autoimmune diseases, including LN. In LN, the NLRP3 inflammasome exerts pathological effects on various renal cells, particularly podocytes and renal tubular cells. Enhanced fluorescence localization and elevated protein expression of the NLRP3 inflammasome (and its core components) can be detected in these cells. It has been established that multiple upstream regulatory factors, including members of the guanylate-binding protein (GBP) family (GBP3, GBP5), CD36, PIM1, IRF2, and S1P, have the capacity to activate the NLRP3 inflammasome and its associated components. This process serves to initiate inflammatory responses and accelerate LN progression. Furthermore, a number of studies have successfully alleviated and treated LN by inhibiting the activation of the NLRP3 inflammasome. This inhibition can be accomplished through two main approaches: the following methods have been employed to increase the expression of endogenous factors such as FGF21 and SIRT1; increasing the expression of endogenous factors exogenously using agents including phytochemicals (e.g.; honokiol, epigallocatechin gallate, procyanidin B2, icaritin, luteolin, the active metabolite M1 of ginsenoside Rg1, ursolic acid, total notoginsenoside saponins, and citral); the NLRP3 inhibitor MCC950, the nuclear factor-κB (NF-κB) inhibitor Bay11-7082; melatonin; xenon; and notoginseng injection. All these strategies improve the progression and prognosis of LN by suppressing the activation of the NLRP3 inflammasome. This article systematically summarizes the composition and activation mechanism of the NLRP3 inflammasome, as well as its activation factors in LN. In addition, it explores treatment strategies for LN targeting the NLRP3 inflammasome, particularly emphasizing the potential therapeutic effects of phytochemicals. This article provides new ideas for the development of LN-related drugs and treatment plans.
- Lupus nephritis /
- Inflammasome /
- Nucleotide-binding oligomerization domain-like receptors family pyrin domain containing 3 /
- Phytochemicals

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图 1 NLRP3炎性小体结构和激活

注：由Figdraw软件绘制。

Figure 1. The structure and activation of the NLRP3 inflammasome

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