外源性酸盐通过巨细胞中依赖HIF-1α的糖解调节来减弱炎症反应
Na Li1, Yi Gong2,3, Yalin Zhu1,4
1Faculty of Anesthesiology, Changhai Hospital (First Affiliated Hospital of Naval Medical University), Naval Medical University, Shanghai, 200433, China.
Cellular and molecular life sciences : CMLS
|December 26, 2024
概括
短期的乙酸盐暴露通过通过HIF-1α抑制巨细胞糖解,从而防止败血症. 这种机制涉及减少的促炎性细胞因子和胰岛素乙化,为急性炎症提供了一种新的治疗途径.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢途径 代谢途径
- 败血症的研究研究.
背景情况:
- 细胞因子风暴是急性炎症性疾病 (如败血症) 的特征.
- 微生物组衍生的短链脂肪酸,如乙酸,影响免疫细胞功能.
- 外源乙对急性炎症,特别是败血症的影响尚不清楚.
研究的目的:
- 为了研究外源性酸盐对败血症的影响.
- 阐明乙酸在急性炎症中的作用的基本机制.
- 探索酸盐在巨细胞代谢和败血症期间免疫反应中的作用.
主要方法:
- 在手术患者和败血症小鼠中观察血清酸盐水平.
- 在体内和体外实验中暴露巨细胞对外源性酸盐的实验.
- 评估糖解,促炎性细胞因子的产生,以及低氧诱导因子1亚单元α (HIF-1α) 的稳定.
- 研究了乙-CoA合成酶-2,GPR41和GPR43.3的作用.
- 分析乙-CoA的产生,基因素乙化和NF-κB p65乙化.
主要成果:
- 血清乙酸盐水平在败血症患者和小鼠中增加.
- 短期,高剂量的外源乙通过抑制巨细胞糖解来保护小鼠免受败血症的影响.
- HIF-1α稳定逆转了乙酸对糖解和细胞因子生产的抑制作用.
- 乙-CoA合成酶-2调解了乙酸的免疫抑制作用.
- 乙酸增加了乙-CoA,促进了基因素乙化,并减少了NF-κB p65乙化.
结论:
- 外源酸盐,特别是在毫米级水平,可以减弱巨细胞在急性炎症期间的免疫反应.
- 乙酸在败血症中的保护作用与抑制HIF-1α依赖的糖解有关.
- 乙通过调节巨细胞代谢和表观遗传修饰来调节炎症反应.
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