由于HIF3α/SIRT1引起的出血性休克和再流引起的认知障碍
Song Xue1, Jinyan Wang1, Yao Tian2
1Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, Hefei, 230601, China.
Free radical biology & medicine
|August 17, 2025
概括
缺氧诱导因子3α (HIF3α) 通过增加神经元亡,恶化脑损伤后的认知障碍. 减少HIF3α可以通过抑制SIRT1依赖的自来防止这种损伤.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 病理学 病理学 病理学
背景情况:
- 大脑缺血-反损伤 (CIRI) 导致神经元亡和认知缺陷.
- 缺氧诱导因子3α (HIF3α) 与认知障碍有关,但其在CIRI中的作用尚不清楚.
研究的目的:
- 调查HIF3α在脑缺血-再输液损伤和相关认知障碍中的作用.
主要方法:
- 用于体外氧气-葡萄糖剥夺/再氧化 (OGD/R) 和体内出血冲击和再注射 (HSR) 模型.
- 检查了SIRT1和HIF3α的同定位,蛋白质表达 (p-tau,LC3B),亡,自和认知功能.
- 利用siRNA介导的HIF3α和SIRT1.1的药理抑制/基因敲除的敲除.
主要成果:
- 在OGD/R模型中,HIF3α敲击降低了SIRT1表达,抑制了自,降低了p-tau,并减弱了神经元亡.
- 在HSR模型中,HIF3α淘汰改善了神经元亡,突触损失和认知缺陷.
- 抑制或淘汰SIRT1并没有影响HIF3α水平,这表明HIF3α在SIRT1.1的上游作用.
结论:
- HIF3α通过促进SIRT1依赖的自,导致海马神经元亡,加剧了与CIRI相关的认知障碍.
- 针对HIF3α可能为CIRI诱导的认知功能障碍提供治疗策略.
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