核苷酸结合寡聚化结构域样受体蛋白3炎性小体在肝脏疾病中的作用机制

杨燕; 葛斐林; 黄倩; 张馨月; 曾锐; 肖小河; 柏兆方; 孙琴

doi:10.3969/j.issn.1001-5256.2022.04.041

核苷酸结合寡聚化结构域样受体蛋白3炎性小体在肝脏疾病中的作用机制

DOI: 10.3969/j.issn.1001-5256.2022.04.041

杨燕^1a,
葛斐林²,
黄倩^1b,
张馨月^1a,
曾锐^1a,
肖小河³,
柏兆方^3, , ,,
孙琴^{1a, 4a, 4b, , ,}

1a.
西南医科大学中西医结合学院, 四川泸州 646000
1b.
西南医科大学药学院, 四川泸州 646000
2.
北京中医药大学中药学院, 北京 100029
3.
解放军总医院第五医学中心全军中医药研究所，北京 100039
4a.
西南医科大学附属中医医院中西医结合药物研究中心, 四川泸州 646000
4b.
西南医科大学附属中医医院国家中医临床研究基地, 四川泸州 646000

基金项目:

国家自然科学基金项目 (8193000309);

四川省科学技术厅项目 (2021YFH0150);

四川省中医药管理局项目 (2017C012)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：杨燕、葛斐林负责起草文章；黄倩、张馨月、曾锐负责收集资料；肖小河、柏兆方、孙琴负责拟定写作思路，修改文章关键内容并最后定稿。

详细信息

通信作者:
柏兆方，baizf2008@hotmail.com

孙琴，zxyjhsq@swmu.edu.cn

杨燕、葛斐林对本文贡献等同,同为第一作者

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出版历程
- 收稿日期: 2021-08-25
- 录用日期: 2021-09-26
- 出版日期: 2022-04-20

Mechanism of action of nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome in liver diseases

Yan YANG^1a,
Feilin GE²,
Qian HUANG^1b,
Xinyue ZHANG^1a,
Rui ZENG^1a,
Xiaohe XIAO³,
Zhaofang BAI^{3
, ,
,},
Qin SUN^{1a, 4a, 4b
, ,
,}

1a.
School of Integrated Traditional Chinese and Western Medicine, Southwest Medical University, Luzhou, Sichuan 646000, China
1b.
School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China
2.
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China
3.
China Military Institute of Chinese Medicine, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
4a.
Drug Research Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
4b.
National Traditional Chinese Medicine Clinical Research Base, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China

Research funding:

National Natural Science Foundation of China (8193000309);

Sichuan Provincial Department of Science and Technology Project (2021YFH0150);

Sichuan Administration of Traditional Chinese Medicine Project (2017C012)

More Information

Corresponding author: BAI Zhaofang, baizf2008@hotmail.com(ORCID: 0000-0002-6208-150X); SUN Qin, zxyjhsq@swmu.edu.cn(ORCID: 0000-0002-4624-8808)

摘要

摘要: 炎症小体在肝脏的天然免疫中发挥着重要作用，然而炎症小体的过度活化能够导致肝脏的炎症损伤，其中NLRP3炎症小体的损伤机制研究最为清楚。研究表明，多种肝脏疾病的发生可能均与炎症小体(尤其NLRP3炎症小体)的过度活化有关。本文将分别从炎症小体、NLRP3炎症小体的活化机制及其在不同肝脏疾病中的作用机制进行综述，以期从NLRP3炎症小体角度，为肝脏疾病的治疗靶点提供参考。
- NLRP3炎症小体 /
- 肝疾病 /
- 免疫, 先天
Abstract: Inflammasomes play an important role in the innate immunity of the liver; however, the excessive activation of inflammasomes can lead to liver inflammation and injury. The mechanism of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome-mediated liver injury has been extensively studied. Related studies have shown that the development of various liver diseases may be associated with the excessive activation of inflammasomes, especially NLRP3 inflammasome. This article reviews inflammasomes, the activation mechanism of NLRP3 inflammasome, and the role of NLRP3 inflammasome in different liver diseases, so as to provide a reference for the treatment targets of liver diseases from the perspective of NLRP3 inflammasome.
- NLRP3 Inflammasome /
- Liver Diseases /
- Immunity, Innate

HTML全文

图 1 NLRP3炎症小体的活化机制示意图

Figure 1. Activation mechanism of NLRP3 inflammasome

下载: 全尺寸图片幻灯片

表 1 NLRP3炎症小体在肝脏疾病中的作用机制小结

Table 1. Summary of the mechanism of NLRP3 inflammasome in liver diseases

肝脏疾病	活化细胞	NLRP3炎症小体在脏病中的机制	参考文献
病毒性肝病(以HBV为代表)	单核巨噬细胞、肝实质细胞	HBX蛋白通过激活NLRP3炎症小体，促进氧化应激而导致肝细胞炎症损伤；HBeAg通过抑制NF-κB通路和ROS的产生，从而抑制NLRP3炎症小体免疫耐受	17-18
ALD	单核巨噬细胞	暴露于酒精的肝脏单核巨噬细胞通过激活NLRP3炎症小体而促进IL-1β的释放，进而募集更多的自然杀伤T淋巴细胞、中性粒细胞；此外，还能通过焦亡影响ALD	21-24
NAFLD	M1型巨噬细胞	通过AMPK/NLRP3/HMGB-1信号通路而缓解IR; IL-18可通过调节内质网应激，减轻肝细胞坏死或凋亡	27-29，34-34
肝纤维化	肝星状细胞、M2型巨噬细胞	肝星状细胞和巨噬细胞通过激活NLRP3小体，释放大量的致炎因子(IL-1β)，从而刺激肝星状细胞的活化和不断增殖	35-37
肝癌	纤维细胞、T淋巴细胞、单核巨噬细胞	IL-1、IL-18等炎症因子促进肿瘤转移基因和生长因子的表达，进而促进肿瘤细胞的黏附和转移；适量的IL-1、IL-18可能促进肿瘤细胞的凋亡进而抑制肿瘤	38-41
DILI	单核巨噬细胞、中性粒细胞	药物对细胞造成损伤而释放损伤相关分子模式(如ROS)，从而促进单核巨噬细胞、中性粒细胞中NLRP3炎症小体的活化，IL-1β释放增多，从而引起肝脏的炎症损伤	43-44

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