整合素CD11b通过小胶质细胞/巨噬细胞极化机制缓解脑缺血/再灌注损伤

IF 2.7 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Gui-Nan Jiang, Qiu-Yue Lin, Xiang-Bo An, Wei-Jia Yu, Jie Bai, Xin Yu, Feng Wang, Hui-Hua Li
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引用次数: 0

摘要

小胶质细胞/巨噬细胞的极化对于维持脑缺血/再灌注(I/R)损伤时的神经炎症反应至关重要。整合素CD11b参与神经炎症、免疫调节和神经损伤修复过程。然而,它在脑I/R损伤期间小胶质细胞和巨噬细胞介导的神经炎症中的作用仍然知之甚少。野生型(WT)、CD11b敲除(KO)或中和抗体处理的小鼠被置于一过性脑动脉I/R损伤(tMCAO)模型中。采用qPCR、免疫荧光和western blotting检测CD11b的表达。H&;E和Nissl染色评价组织病理学特征,DHE染色检测ROS生成,TUNEL检测神经元凋亡,免疫荧光染色评价小胶质细胞极化。我们发现,缺血半暗区在tMCAO后CD11b显著升高。CD11b KO可显著减轻缺血半暗区tmcao诱导的梗死、神经功能缺损、氧化应激和神经元凋亡。此外,CD11b KO显著增强了小胶质细胞/巨噬细胞的抗炎表型转变,导致炎症加速消退。此外,CD11b的药物阻断显示出与CD11b KO相似的保护作用。同时,CD11b缺乏显著抑制p-p65/p-STAT1信号通路的激活,上调p-STAT6的表达。综上所述,CD11b通过调节小胶质细胞和巨噬细胞极化来预防脑I/R损伤,从而减少随后的神经炎症和神经元死亡。我们的研究结果表明,CD11b干预可能是急性缺血性脑卒中的一种潜在治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Integrin CD11b Alleviates Cerebral Ischemia/Reperfusion Injury via a Mechanism Involving Microglia/Macrophage Polarization

The polarization of microglia/macrophages is crucial for maintaining the neuroinflammatory response during cerebral ischemia/reperfusion (I/R) injury. Integrin CD11b is implicated in the processes of neuroinflammation, immune regulation, and nerve injury repair. However, its role in microglia- and macrophage-mediated neuroinflammation during cerebral I/R injury remains poorly understood. Wild-type (WT), CD11b knockout (KO), or neutralizing antibody-treated mice were subjected to a transient cerebral artery I/R injury (tMCAO) model. CD11b expression was detected by qPCR, immunofluorescence, and western blotting. Histopathological features were evaluated by H&E and Nissl staining, ROS production was detected by DHE staining, neuronal apoptosis was detected by TUNEL assays, and microglia polarization was evaluated by immunofluorescence staining. We discovered that CD11b was significantly increased in the ischemic penumbra following tMCAO. CD11b KO significantly alleviated tMCAO-induced infarct, neurological deficits, oxidative stress, and neuronal apoptosis in the ischemic penumbra. Moreover, CD11b KO significantly enhanced the anti-inflammatory phenotype transition of microglia/macrophages, leading to accelerated inflammation resolution. Furthermore, pharmacological blockade of CD11b demonstrated a protective effect similar to that of CD11b KO. Meanwhile, CD11b deficiency significantly inhibited the activation of p-p65/p-STAT1 signaling pathway and upregulated p-STAT6 expression. In conclusion, CD11b protects against cerebral I/R injury by modulating microglial and macrophage polarization, thereby reducing subsequent neuroinflammation and neuronal death. Our findings suggest that CD11b intervention could be a potential therapeutic strategy for acute cerebral ischemic stroke.

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来源期刊
Journal of Molecular Neuroscience
Journal of Molecular Neuroscience 医学-神经科学
CiteScore
6.60
自引率
3.20%
发文量
142
审稿时长
1 months
期刊介绍: The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.
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