在ICH之后,HMGB1/TLR4轴通过激活NLRP3炎症酶激活火
Chunyan Lei1, Keyang Chen1, Yu Gu1
1From the First Department of Neurology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China.
Journal of neuroimmunology
|July 12, 2024
概括
高流动性组盒1 (HMGB1) 和类似收费受体4 (TLR4) 信号激活NLRP3炎症体,导致脑内出血后的热和脑损伤. 抑制这种途径可能会带来治疗效益.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 病理学 病理学 病理学
背景情况:
- HMGB1/TLR4轴与急性脑内出血 (ICH) 引起的炎症有关.
- 神经质炎症和神经炎症是急性ICH阶段的关键特征.
研究的目的:
- 为了调查HMGB1/TLR信号是否激活ICH后的炎症体和热.
- 探索NLRP1和NLRP3炎症酶在ICH诱导的热死中的作用.
主要方法:
- 在Sprague-Dawley大鼠中通过自身血液注射诱导ICH.
- 评估了神经系统缺陷,并分析了NLRP1/NLRP3炎症体,烧死标记物和相关蛋白质.
- 干预组接受了针对NLRP1/NLRP3,HMGB1抑制剂 (乙烯酸盐) 或TLR4抑制剂 (TAK-242) 的siRNA.
主要成果:
- ICH在条形体中对NLRP1和NLRP3进行了上调,增加了灭阳性细胞和相关蛋白质水平 (caspase-1,ASC,IL-1β).
- 抑制NLRP1/NLRP3或抑制HMGB1/TLR4,部分逆转热和神经缺陷.
- 抑制HMGB1/TLR4降低了NLRP3,但没有NLRP1.
结论:
- 在急性ICH期间,HMGB1/TLR4信号可能会激活NLRP3炎症酶,从而导致热亡和随后的组织损伤.
- 准HMGB1/TLR4/NLRP3通路是缓解出血性中风后神经系统缺陷的潜在治疗策略.
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