通过NLRP3激活来破坏血脑屏障,由肠球菌衍生的细胞解酶会加剧缺血性中风
Jia-Ni Huang1, Wei-Hao Zhuang1, Yi-Si Lin2
1Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
Journal of neuroinflammation
|November 11, 2025
概括
菌细胞素 (Enterococcus cytolysin) 通过NLRP3炎症酶激活,通过破坏血脑屏障 (BBB) 恶化缺血性中风. 抑制NLRP3为中风患者提供了一个有希望的神经保护策略.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
背景情况:
- 缺血性中风是一个重要的全球健康问题.
- 在中风患者的肠道中发现的肠球菌 (Enterococcus) 产生细胞毒素 (cytolysin),这种毒素可以破坏细胞膜.
- 肠道屏障的破坏可能会让细胞素进入血液循环,可能会损害血脑屏障 (BBB).
研究的目的:
- 通过NLRP3炎症酶激活来研究Enterococcus中的细胞素如何破坏BBB.
- 为了确定缺血性中风的潜在治疗点.
主要方法:
- 使用16S rRNA测序和qPCR对100名中风患者的直肠拭子进行分析.
- 用bEnd.3细胞在小鼠和体外研究中的光血性中风模型来评估细胞解酶对BBB完整性和NLRP3激活的影响.
- 评估BBB的透性,肠道屏障功能和NLRP3通路的激活 (RNA测序,qPCR,西部斑点,ELISA).
- 用NLRP3抑制剂MCC950来确认该通路的功能作用.
主要成果:
- 在中风患者中,升的Enterococcus和cylA基因水平与增加的死亡率相关.
- 阳性Cytolysin的Enterococcus通过增加BBB的透性,在小鼠中恶化了中风的严重程度.
- 赛托利辛激活了NLRP3炎酶介导的热,进一步损害了BBB的完整性.
- 赛托利辛破坏了肠道屏障,可能促进了其循环,并导致BBB损伤.
- 使用MCC950抑制NLRP3可减少神经系统缺陷并恢复BBB完整性.
结论:
- 赛托利辛通过NLRP3激活和破坏肠道屏障来破坏BBB,从而加剧缺血性中风.
- 向细胞素和NLRP3是一个有前途的治疗策略,用于缺血性中风的神经保护.
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