低血压缺氧驱动的能量代谢障碍促进了血管内皮功能障碍
Yuyu Zhang1, Jinghuan Wang1, Mengting He1
1Phenome Research Center of TCM, Department of Traditional Chinese Medicine, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, China.
Redox biology
|May 20, 2025
概括
低血压缺氧通过改变能量代谢来破坏血管内皮功能,导致乳酸积累和细胞损伤. 针对酸盐-乳酸盐轴可以防止这种损伤.
科学领域:
- 生理学 生理学 生理学
- 分子生物学分子生物学
- 高度医学 高度医学
背景情况:
- 高原环境会导致低氧,破坏新陈代谢平衡,并导致高山疾病.
- 血管内皮细胞对于血管平衡至关重要,但低氧对其能量代谢和功能的影响尚未完全理解.
研究的目的:
- 研究缺氧诱导的能量代谢变化如何影响血管内皮细胞的稳定性和功能.
- 为了确定将低氧,新陈代谢和血管功能障碍联系在一起的分子机制.
主要方法:
- 采用了综合的转录组和有针对性的代谢组分析.
- 研究了乳酸生产和PKM2乳化在缺氧诱导的血管内皮功能障碍中的作用.
主要成果:
- 缺氧会将内皮细胞的新陈代谢转向糖解,增加乳酸的产生.
- 乳酸过载会触发PKM2乳化,稳定PKM2并加剧线粒体崩和血管功能障碍.
- 阻断酸盐-乳酸盐轴可以在缺氧下保持内皮功能.
结论:
- 缺氧通过能量代谢失调诱导血管内皮功能障碍,特别是通过pyruvate-lactate-PKM2轴.
- 酸盐-乳酸盐轴代表了在低氧条件下预防血管疾病的潜在治疗点.
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