通过向能量代谢重编程,改善因缺血再输血引起的急性损伤
Limei Zhao1, Tingting Zhang1, Zhibo Zhao2
1The Fifth Clinical Medical College of Shanxi Medical University, Xinjian South Road No. 56, Yingze District, Taiyuan 030001, Shanxi, China.
International journal of biological macromolecules
|August 27, 2025
概括
通过恢复脂肪酸氧化 (FAO) 和减少管状上皮细胞 (TEC) 的糖解,肌肉分泌的蛋白质虹膜改善急性损伤 (AKI). 它通过整合蛋白αVβ5受体作用,调节AMPK/ mTOR通路,以防止缺血再输液损伤.
科学领域:
- 肝脏病学
- 代谢途径
- 细胞能量平衡
背景情况:
- 管状上皮细胞 (TEC) 依赖脂肪酸氧化 (FAO) 来获得能量,但在缺血-再输液 (I/ R) 诱导的急性损伤 (AKI) 期间,这种功能受损.
- 这种能量缺陷将TEC代谢从FAO转移到糖解,导致细胞损伤,再生受损,并可能导致慢性病 (CKD) 的进展.
- 已知Irisin能调节能量代谢,并且在糖尿病病等疾病中具有有益作用.
研究的目的:
- 通过纠正脏TEC中的代谢功能障碍来改善I/ R诱导的AKI.
- 阐明在AKI中依赖于素保护作用的特定分子机制,重点关注其受体和下游信号通路.
- 确定AMPK/mTOR途径和HIF-1α在素的脏保护作用中的作用.
主要方法:
- 使用了体外 (HK-2细胞的低氧/低氧化) 和体内 (I/R诱导的AKI模型) 实验.
- 进行了生物信息学分析以确定潜在的分子标和相互作用,包括AMPK (PRKAA2) 和mTOR.
- 实验包括评估素,抗整合素αVβ5抗体以及AMPK和mTOR调节剂对细胞代谢和AKI标志物的影响.
主要成果:
- 在I/ R后,Irisin治疗纠正了TEC的代谢障碍,增强了FAO并降低了糖解,从而改善了I/ R诱导的AKI.
- 虹膜蛋白与整合蛋白αVβ5受体结合,该受体在低氧/低氧化后在TEC上升调节.
- 激素激活AMPK酸化,抑制mTOR酸化,并降低HIF- 1α表达,而阻断整合蛋白αVβ5或调节AMPK/ mTOR通路则取消了这些作用.
结论:
- 通过向TEC上的整合蛋白αVβ5受体,在I/ R诱导的AKI中产生脏保护作用.
- 调节AMPK/mTOR通路并随后调节FAO和糖解是伊丽素改善AKI的关键机制.
- 此外,HIF- 1α在素调节过程中发挥作用,对损伤的整体有益影响有所贡献.
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