药理上抑制cGAS可以通过抑制caspase-3/GSDME-依赖性热致死来改善术后认知功能障碍
Xueshan Bu1, Ping Gong2, Lei Zhang1
1Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China.
Neurochemistry international
|June 6, 2024
概括
抑制cGAS-STING通路可以减少手术后的神经炎症和认知衰退. 这种方法减轻了热,为术后认知功能障碍 (POCD) 提供了潜在的治疗方法.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
背景情况:
- 神经炎症显著导致手术后认知功能障碍 (POCD).
- 循环GMP-AMP合成酶刺激干扰素基因 (cGAS-STING) 途径与神经炎症有关,但其在POCD中的作用尚不清楚.
研究的目的:
- 研究cGAS-STING通路在POCD病变发生过程中的作用.
- 在POCD小鼠模型中评估cGAS抑制的治疗潜力.
主要方法:
- 一个POCD小鼠模型被诱导使用异氨酸麻醉和腹腔切除术.
- 用cGAS抑制剂 (RU.521) 或caspase-3激活剂 (Raptinal) 治疗小鼠和BV2细胞.
- 认知功能,神经炎症标志物和烧死指标使用行为测试,西部斑点,ELISA和TUNEL染色进行了评估.
主要成果:
- 异黄/拉巴罗托米增加了cGAS水平和细胞质dSDNA积累.
- RU.521治疗改善了认知功能,减少了炎症性细胞因子 (TNFα,IL-6) 和抑制了 pyroptosis 标记物 (切割 caspase-3,N-GSDME,IL-1β,IL-18).
- RU.521的保护作用被Raptinal扭转了.
结论:
- 在POCD的发展中,cGAS-STING途径起着至关重要的作用.
- 药理上抑制cGAS可通过抑制caspase-3/GSDME依赖性质炎症来缓解POCD中的神经炎症和认知障碍.
- 准cGAS途径为POCD提供了一个有希望的治疗策略.
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