内皮TLR4和微生物组驱动大脑洞腔形
Alan T Tang1, Jaesung P Choi2, Jonathan J Kotzin3,4
1Department of Medicine and Cardiovascular Institute, University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, Pennsylvania 19104, USA.
Nature
|May 11, 2017
概括
大脑洞腔形与托尔类受体4 (TLR4) 和肠道细菌有关. 阻止TLR4或改变微生物组可能为这种中风和发作提供新的治疗方法.
科学领域:
- 神经科学
- 免疫学
- 微生物学
背景情况:
- 脑腔形 (CCM) 是导致中风和的脑血管病变.
- 目前尚无针对CCM的治疗方法,因此需要对潜在的致病机制进行研究.
- 在CCM中涉及的MEKK3-KLF2/4信号通路的上游激活器仍然在很大程度上未被确定.
研究的目的:
- 在脑洞形中识别疾病路径的上游激活剂.
- 研究内皮类似受体4 (TLR4) 和肠道微生物组在CCM病变发生过程中的作用.
- 探索针对已确定的途径的潜在治疗策略.
主要方法:
- 使用CCM的小鼠模型.
- 研究了托尔类受体4 (TLR4) 激活和阻断的影响.
- 检查了无细菌条件和抗生素治疗对CCM形成的影响.
- 分析了人类遗传数据,以确定多态和CCM病变负担之间的关联.
主要成果:
- 格拉姆阴性细菌或脂多糖的内皮TLR4激活加速了CCM的形成.
- 对TLR4信号的遗传或药理阻断会阻止小鼠的CCM发展.
- 没有细菌的小鼠受到CCM形成的保护,而抗生素治疗改变了敏感性.
- 人类TLR4和CD14的遗传多态性与CCM病变负担的增加相关.
结论:
- 内皮TLR4和肠道微生物组是脑洞形形成的关键刺激剂.
- 针对TLR4信号和微生物组为CCM提供了一种新的治疗策略.
- 天生的免疫信号和微生物组在脑血管疾病的发病过程中起着意想不到的作用.
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