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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

引用本文:
Citation:

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
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

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

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
  • 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。

     

  • 图  1  NLRP3炎症小体的活化机制示意图

    Figure  1.  Activation mechanism of NLRP3 inflammasome

    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 27-2934-34
    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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  • 收稿日期:  2021-08-25
  • 录用日期:  2021-09-26
  • 出版日期:  2022-04-20
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