内皮细胞的高糖溶解导致内皮损伤和腹膜透析中的微血管变化
Zekun Si1, Wenyan Su1, Zhuoyu Zhou1
1Division of Nephrology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Nephrology, Guangdong Provincial Clinical Research Center for Kidney Disease, Nanfang Hospital, Southern Medical University, Guangzhou, P. R. China.
Clinical and translational medicine
|December 1, 2023
概括
腹膜透析 (PD) 中的内皮细胞 (EC) 功能障碍与糖分分解的增加有关. 通过PFKFB3抑制EC糖解可以保护腹膜免受损伤,为PD患者提供潜在的治疗策略.
科学领域:
- 细胞生物学 细胞生物学
- 腎臟醫學 腎臟醫學
- 代谢过程中的代谢.
背景情况:
- 内皮细胞 (EC) 功能障碍和微血管变化是围透析 (PD) 技术失败的关键.
- 在PD中驱动EC功能障碍的精确机制在很大程度上仍未定义.
研究的目的:
- 在小鼠PD模型中研究腹ECs的代谢概况.
- 探索EC糖解,特别是PFKFB3在PD相关的微血管变化中的作用.
- 评估在PD中准EC糖解的治疗潜力.
主要方法:
- 在小鼠PD模型中,结合RNA测序和代谢物集分析.
- 在EC中,对6-果糖-2-激酶/果糖-2,6-双酸酶3 (PFKFB3) 的遗传和药理抑制.
- 从末期病 (ESKD) 患者获得的人类腹组织的分析.
主要成果:
- 在PD模型中的腹膜EC表现出高糖解,将代谢物转移到核酸合成,并促进活性表型 (增殖,透性,炎症).
- 通过抑制PFKFB3来降低EC糖解,改善了PD液体诱导的微血管损伤,包括毛细血管密度,透性和单细胞扩散.
- 增加EC PFKFB3表达与人体ESKD样本中的微血管变化和腹功能障碍相关.
结论:
- 在ECs中的糖溶解在PD期间关键调解腹功能恶化.
- 针对EC糖解,特别是PFKFB3,为PD患者提供了一个有前途的治疗途径,以防止腹损伤.
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