乙酸 (EPA) 通过PPARα-NF-κB轴减轻LPS诱导的氧化应激
Haya AlAbduljader1, Halemah AlSaeed2, Amenah Alrabeea3
1Animal and Imaging Core Facility, Dasman Diabetes Institute, Kuwait City, Kuwait.
Oxidative medicine and cellular longevity
|June 18, 2025
概括
乙酸 (EPA) 通过激活独立于TLR4信号的FABP5/PPARα通路来减少巨细胞的炎症和氧化应激. 这为与慢性炎症相关的代谢障碍提供了潜在的治疗益处.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢健康 代谢健康
- 分子生物学分子生物学
背景情况:
- 由脂聚糖 (LPS) 驱动的代谢性内毒性,导致肥胖和2型糖尿病的慢性炎症和胰岛素抵抗.
- 在巨细胞上通过LPS激活托尔类受体4 (TLR4),触发了促炎性细胞因子的释放,加剧了代谢功能障碍.
- 乙酸 (EPA;C20:5 (n-3)),一种omega-3脂肪酸,具有抗炎性质,但其针对LPS诱导的压力的精确机制尚未完全理解.
研究的目的:
- 阐明EPA缓解LPS诱导的氧化应激和巨细胞炎症的分子途径.
- 调查EPA在调节内细胞网膜 (ER) 压力,氧化损伤和炎症信号传递中的作用.
主要方法:
- 在LPS刺激之前,巨细胞被EPA预处理.
- 评估了关键的炎症标志物 (IL-1β,IL-6,HLA-DR),ER压力标志物 (ATF4,DDIT3,HSPA5/GRP78,BIP,CHOP) 和氧化压力标志物 (HIF1α,ROS,线粒体膜潜力).
- 使用抑制剂GW9662研究了PPARα的参与,并分析了NF-κB和TLR4-IRF5通路.
主要成果:
- EPA预处理显著降低了LPS诱导的IL-1β和IL-6的表达和分泌,并降低了HLA-DR巨细胞.
- 环保署减轻了ER压力和氧化压力,主要压力标志物的表达减少和线粒体功能的保存证明了这一点.
- 美国环保署增加了PPARα和FABP5的表达,抑制了独立于TLR4-IRF5的NF-κB激活,其影响被PPARα抑制取消了.
结论:
- 乙酸通过FABP5/PPARα/NF-κB轴调节LPS诱导的氧化应激和巨细胞炎症,独立于TLR4-IRF5信号传输.
- 这些发现揭示了EPA抗炎作用的新机制.
- 针对FABP5/PPARα通路,为具有慢性炎症特征的代谢障碍提供了潜在的治疗策略.
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