乳酸通过OXPHOS和Cebpb驱动M2极化,并加速外围神经再生
Wei Li1, Xiao Wang1, Xiaoli Liu1
1Department of Immunology, School of Basic Medicine, Qingdao University, Qingdao, Shandong 266071, China.
International immunopharmacology
|March 12, 2026
概括
低剂量的乳酸盐通过增强氧化酸化促进M1-M2巨细胞转换以修复神经. 高剂量的乳酸盐会破坏线粒体的功能,阻碍再生. 这突出了乳酸盐的含量.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 代谢过程中的代谢.
背景情况:
- 持续的炎症会阻碍周围神经的再生.
- 巨细胞,特别是M1和M2表型,在神经修复中至关重要.
- 驱动M1-M2巨细胞过渡的因素尚不清楚.
研究的目的:
- 调查乳酸在调节外围神经再生期间巨细胞极化中的作用.
- 确定乳酸盐的最佳度,以促进M1-M2巨细胞过渡和神经修复.
主要方法:
- 坐骨神经损伤模型在体内.
- 用斯万细胞和巨细胞进行体外研究.
- 乳酸盐度的测量. 乳酸盐度的测量.
- 巨细胞极化分析 (M1/M2标记物).
- 转录基因分析 (RNA测序).
- 对代谢活动进行海马分析和ATP量化.
- 反应性氧物种 (ROS) 和线粒体膜潜力的评估.
主要成果:
- 乳酸水平与神经损伤后的M2巨细胞积累相关.
- 低剂量的乳酸盐 (10-20mM) 增强了M2极化,加速了神经的再生.
- 高剂量的乳酸盐 (50毫米) 并没有改善再生,并诱导线粒体功能障碍.
- 在M1巨细胞中,乳酸上调M2标记物 (Arg1,VEGF,TGF-β) 和氧化酸化 (OXPHOS) 基因.
- 乳酸酸激活了OXPHOS和ATP的产生.
- 鉴定出CCAAT/增强剂结合蛋白β (Cebpb) 是一个关键的转录因子.
结论:
- 低剂量的乳酸盐通过OXPHOS代谢重编程和Cebpb上调促进M1-M2巨细胞的过渡.
- 过度的乳酸破坏了线粒体功能,损害了神经的再生.
- 乳酸度依赖调节巨细胞极化,为神经修复的代谢调节提供了洞察力.
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