Advances of NLRP3 Inflammasome in Post-stroke Cognitive Impairment

doi:10.12114/j.issn.1007-9572.2022.0609

Abstract

Abstract:

A common complication of stroke patients is post-stroke cognitive impairment (PSCI) , which significantly reduces their quality of life. There are no effective targeted treatment measures currently available for PSCI in clinical practice. A large number of studies have already indicated that the activation of NLRP3 inflammasome plays a crucial role in PSCI, and many inhibitory treatments have been shown to improve cognitive impairment. The purpose of this study was to summarized the activation and modulating factors of NLRP3 inflammatory bodies and the relationship with PSCI. Some studies have been demonstrated that inhibiting NLRP3 or its associated inflammatory body components reduces the inflammatory response, promoting cognitive function recovery in cell and animal models of PSCI. Consequently, targeting NLRP3 inflammatory bodies may be a new trends of dealing with PSCI treatment. Despite the fact that numerous drugs and therapeutic measures have been proved to suppress the activation of NLRP3 inflammatory bodies, their clinical efficacy and safety have not yet been confirmed.

Key words: Cognition disorders, Stroke, Post-stroke cognitive impairment, NLRP3 inflammasome, Neuroinflammation, Mitochondrial dysfunction, Review

摘要：

脑卒中后认知障碍（PSCI）是脑卒中患者常见的并发症，严重影响患者的生活质量。目前，PSCI在临床治疗中尚未发现有效的针对性治疗措施。大量研究证实核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）炎症小体的活化在PSCI中起关键作用，且对其进行的许多抑制性治疗显示出了改善认知障碍的功效。为此，本文总结了NLRP3炎症小体的活化和影响因素及其与PSCI的关系，发现在PSCI的细胞和动物模型中，针对NLRP3或其炎症小体成分的抑制措施可以减轻炎性反应和相应的病理特征，从而促进其认知功能的恢复，因此，靶向NLRP3炎症小体可能是PSCI治疗的新趋势。然而到目前为止，尽管许多药物和治疗措施已成功鉴定出能够抑制NLRP3炎症小体的活化，但其在临床中的治疗效果和安全性仍有待进一步验证。

关键词: 认知障碍, 卒中, 脑卒中后认知障碍, 核苷酸结合寡聚化结构域样受体蛋白3炎症小体, 神经炎症, 线粒体功能障碍, 综述

LI Xiaoxiao,BAI Yanjie,WANG Yan, et al. Advances of NLRP3 Inflammasome in Post-stroke Cognitive Impairment[J]. Chinese General Practice, 2023, 26(17): 2176-2182. DOI: 10.12114/j.issn.1007-9572.2022.0609.
李晓晓,白艳杰,王岩等. 核苷酸结合寡聚化结构域样受体蛋白3炎症小体在脑卒中后认知障碍中的研究进展[J]. 中国全科医学, 2023, 26(17): 2176-2182. DOI: 10.12114/j.issn.1007-9572.2022.0609.

Figures/Tables 3

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第一作者	发表年份（年）	研究类型	主要结果
MATSUYAMA^[44]	2020	动物实验	NLRP3炎症小体、IL-18、IL-1β均上调
LI^[45]	2022	细胞实验	NLRP3、ASC、caspase-1、IL-1β、IL-18均上调
吴金波^[46]	2021	临床研究	NLRP3 mRNA上调
李国丽^[47]	2022	临床研究	NLRP3、IL-1β、IL-18均上调
赵凤华^[48]	2021	临床研究	NLRP3、ASC、caspase-1、IL-1β均上调

第一作者	发表年份（年）	研究类型	主要结果
MATSUYAMA^[44]	2020	动物实验	NLRP3炎症小体、IL-18、IL-1β均上调
LI^[45]	2022	细胞实验	NLRP3、ASC、caspase-1、IL-1β、IL-18均上调
吴金波^[46]	2021	临床研究	NLRP3 mRNA上调
李国丽^[47]	2022	临床研究	NLRP3、IL-1β、IL-18均上调
赵凤华^[48]	2021	临床研究	NLRP3、ASC、caspase-1、IL-1β均上调

第一作者	发表年份（年）	研究类型	干预方式	治疗作用机制
LI^[5]	2020	动物实验	MCC950	阻断NLRP3寡聚化和形成，减少小胶质细胞数量，增加神经元数量，促进海马神经发生
WANG^[50]	2017	动物实验	DY-9836	抑制亚硝化应激和NLRP3信号传导
FENG^[51]	2021	动物实验	miR-138-5p	与NLRP3特异性相互作用，改善神经炎症
ZHANG^[52]	2021	动物+细胞实验	牡荆素	抑制NLRP3炎症小体介导的炎性反应
ZHANG^[53]	2020	动物实验	Kellerin	抑制NLRP3炎症小体通路的激活，调节小胶质细胞的极化
LI^[54]	2017	动物实验	黄芪甲苷	控制ROS的产生来抑制NLRP3炎症小体活化，降低海马中小胶质细胞的过度激活和炎性细胞因子的过度表达
LIU^[56]	2020	动物实验	蛇床子素	改善海马神经元损伤，抑制小胶质细胞活化，并通过抑制NLRP3炎症小体活化减少海马中的Aβ沉积
BANG^[4]	2019	动物实验	梅素	抑制神经胶质增生并减弱NLRP3和NF-κB的激活
SHI^[57]	2021	网络药理学和分子对接	益智通脉汤	抑制NLRP3炎症小体、TNF信号通路和toll样受体信号通路
XIA^[58]	2019	动物实验	小脑顶核电刺激	下调NLRP3、caspase-1、IL-1β、IL-18的表达，抑制自噬过程和炎性反应，从而减轻神经元的凋亡
DU^[59]	2018	动物实验	针刺足三里和百会穴	减少海马神经元丢失和氧化应激，降低硫氧还蛋白相互作用蛋白、NLRP3、caspase-1和IL-1β的表达
ZHONG^[60]	2022	动物实验	电针神庭和百会穴	上调线粒体自噬相关蛋白和抑制ROS诱导的NLRP3炎症小体活化发挥神经保护作用

第一作者	发表年份（年）	研究类型	干预方式	治疗作用机制
LI^[5]	2020	动物实验	MCC950	阻断NLRP3寡聚化和形成，减少小胶质细胞数量，增加神经元数量，促进海马神经发生
WANG^[50]	2017	动物实验	DY-9836	抑制亚硝化应激和NLRP3信号传导
FENG^[51]	2021	动物实验	miR-138-5p	与NLRP3特异性相互作用，改善神经炎症
ZHANG^[52]	2021	动物+细胞实验	牡荆素	抑制NLRP3炎症小体介导的炎性反应
ZHANG^[53]	2020	动物实验	Kellerin	抑制NLRP3炎症小体通路的激活，调节小胶质细胞的极化
LI^[54]	2017	动物实验	黄芪甲苷	控制ROS的产生来抑制NLRP3炎症小体活化，降低海马中小胶质细胞的过度激活和炎性细胞因子的过度表达
LIU^[56]	2020	动物实验	蛇床子素	改善海马神经元损伤，抑制小胶质细胞活化，并通过抑制NLRP3炎症小体活化减少海马中的Aβ沉积
BANG^[4]	2019	动物实验	梅素	抑制神经胶质增生并减弱NLRP3和NF-κB的激活
SHI^[57]	2021	网络药理学和分子对接	益智通脉汤	抑制NLRP3炎症小体、TNF信号通路和toll样受体信号通路
XIA^[58]	2019	动物实验	小脑顶核电刺激	下调NLRP3、caspase-1、IL-1β、IL-18的表达，抑制自噬过程和炎性反应，从而减轻神经元的凋亡
DU^[59]	2018	动物实验	针刺足三里和百会穴	减少海马神经元丢失和氧化应激，降低硫氧还蛋白相互作用蛋白、NLRP3、caspase-1和IL-1β的表达
ZHONG^[60]	2022	动物实验	电针神庭和百会穴	上调线粒体自噬相关蛋白和抑制ROS诱导的NLRP3炎症小体活化发挥神经保护作用