激活LPS的酶乙基酸酸酶可以保护大脑免受实验中风的伤害
Yuanbo Zhu1, Yue Hu1, Zhongwang Liu1
1Department of Translational Neuroscience, Jing'an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China.
概括
在缺血性中风后,乙酸酸酶 (AOAH) 调节炎症和血脑屏障 (BBB) 完整性. 由于增加中性粒细胞透,AOAH缺乏会使中风的结果恶化,而AOAH过度表达则具有保护作用.
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:
- 血脑屏障 (BBB) 的破坏和炎症是缺血性中风发病的关键特征.
- 脂多糖 (LPS),由乙氧基酶 (AOAH) 调节,与急性中风有关.
- 在此之前,AOAH在缺血性中风病理生理学中的特定作用是未知的.
研究的目的:
- 调查AOAH在中性粒细胞扩散,BBB中断和缺血性中风后脑梗塞中的作用和机制.
- 为了确定AOAH是否调节炎症反应和中风严重程度.
主要方法:
- 在体内实验中,使用过渡焦点脑缺血的小鼠模型进行实验.
- 分析心脏病附近地区中性粒细胞中AOAH表达的分析.
- 评估中性粒细胞扩散,BBB完整性,细胞因子产量和野外类型和Aoah淘汰赛小鼠的心脏病体积.
- 调查托尔类受体4 (TLR4) 和中性粒细胞贩运途径 (LFA-1) 的作用.
主要成果:
- 经过缺血性中风后,心脏中风周围区域中性粒细胞的AOAH被上调.
- 缺少AOAH加剧了中性粒细胞扩散,增加了促炎性细胞因子,加剧了BBB干扰,并导致中风结果较差.
- 在Aoah淘汰赛小鼠中,这些有害影响依赖于托尔类受体4 (TLR4) 信号传递.
- 中性粒细胞枯竭或LFA-1抑制显著降低了Aoah淘汰赛小鼠中的BBB分解.
- 过度表达AOAH减少了中性粒细胞的招募,BBB损伤和心脏病发作量.
结论:
- AOAH在调节中性粒细胞依赖的BBB分解和缺血性中风中脑梗塞方面发挥着至关重要的作用.
- 缺少AOAH会加剧中风损伤,而过度表达AOAH会提供保护.
- 调节AOAH活性为缺血性中风治疗提供了一个潜在的新疗法策略.
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