中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (3): 603-608.doi: 10.4103/1673-5374.350204

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

β2M参与脑卒中的发生发展与神经炎症的关系

  

  • 出版日期:2023-03-15 发布日期:2022-08-28
  • 基金资助:

    中国国家自然科学基金项目(81771337

β2-Microglobulin exacerbates neuroinflammation, brain damage, and cognitive impairment after stroke in rats

Feng Chen1, Jing Liu2, 3, Fa-Qiang Li1, Shuai-Shuai Wang1, Yan-Yan Zhang1, Yun-Yun Lu1, Fang-Fang Hu1, Rui-Qin Yao2, *   

  1. 1Department of Neurology, Xuzhou Cancer Hospital, Xuzhou, Jiangsu Province, China; 2Department of Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu Province, China; 3Department of Neurology, Xuzhou No. 1 People’s Hospital, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China
  • Online:2023-03-15 Published:2022-08-28
  • Contact: Rui-Qin Yao, PhD, wenxi_yao@163.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 81771337 (to RQY).

摘要:

β2-微球蛋白是主要组织相容性复合体I类分子的轻链成分之一,与衰老相关的认知障碍和阿尔茨海默病有关。尽管有研究认为β2M上调与缺血性脑卒中高度相关,但其具体的作用尚不明朗。因此,此次实验利用大脑中动脉栓塞方法法制作了局灶性脑缺血大鼠模型,发现在脑卒中急性期,脑脊液、血清和脑组织中β2-微球蛋白均显著增加,而恢复期其水平则逐渐下降。继而以干扰RNA抑制脑卒中急性期β2-微球蛋白的表达,TTC染色和Morris水迷宫结果发现β2-微球蛋白降低不但可缩小脑卒中大鼠的脑梗死体积,还可改善其认知功能。但是值得注意的是,β2-微球蛋白也可抑制制胶质细胞和NLRP3炎性小体活化,以及caspase-1 (p20)、白细胞介素1β、白细胞介素6和肿瘤坏死因子α等炎性因子的产生。因而提示,β2M可通过激活NLRP3炎症小体相关的神经炎症参与脑卒中中的脑损伤和认知障碍。

https://orcid.org/0000-0001-7617-5438 (Rui-Qin Yao)


关键词:

脑卒中, 脑缺血, 大脑中动脉闭塞, β2-微球蛋白, NLRP3炎症小体, 神经炎症, 胶质细胞激活, 认知障碍, 认知改善, 梗死体积

Abstract: β2-Microglobulin (β2M), a component of the major histocompatibility complex class I molecule, is associated with aging-related cognitive impairment and Alzheimer’s disease. Although upregulation of β2M is considered to be highly related to ischemic stroke, the specific role and underlying mechanistic action of β2M are poorly understood. In this study, we established a rat model of focal cerebral ischemia by occlusion of the middle cerebral artery. We found that β2M levels in the cerebral spinal fluid, serum, and brain tissue were significantly increased in the acute period but gradually decreased during the recovery period. RNA interference was used to inhibit β2M expression in the acute period of cerebral stroke. Tissue staining with 2,3,5-triphenyltetrazolium chloride and evaluation of cognitive function using the Morris water maze test demonstrated that decreased β2M expression in the ischemic penumbra reduced infarct volume and alleviated cognitive deficits, respectively. Notably, glial cell, caspase-1 (p20), and Nod-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation as well as production of the inflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α were also effectively inhibited by β2M silencing. These findings suggest that β2M participates in brain injury and cognitive impairment in a rat model of ischemic stroke through activation of neuroinflammation associated with the NLRP3 inflammasome.

Key words: cognitive impairment, cognitive improvement, glial activation, infarct volume, ischemia, middle cerebral artery occlusion, neuroinflammation, NLRP3 inflammasome, stroke, β2 microglobulin