IGF-1通过调节FOXO1表达来调节风扇诱导的隔膜功能障碍中的骨肌肉退化和重塑
Luyu Yang1, Xiaohong Jiang2, Shouzhi Fu1
1Department of ICU/Emergency, Wuhan Third Hospital & Tongren Hospital of Wuhan University, 430070 Wuhan, Hubei, China.
Discovery medicine
|February 27, 2024
概括
胰岛素样生长因子-1 (IGF-1) 通过减少肌肉分解,保护免受呼吸器诱导的隔膜功能障碍 (VIDD). 上调IGF-1降低FOXO1的调节,缓解肌肉缩并帮助VIDD的肌肉重塑.
科学领域:
- 生理学 生理学 生理学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 机械通风 (MV) 对重症患者至关重要,但可能导致呼吸器诱导的腹膜功能障碍 (VIDD),导致呼吸肌缩.
- 胰岛素样生长因子-1 (IGF-1) 对于骨肌肉的调节至关重要,而分叉盒蛋白O1 (FOXO1) 则与肌肉缩有关.
研究的目的:
- 研究IGF-1对VIDD肌肉退化和重塑的影响.
- 探索在VIDD中涉及FOXO1的潜在机制.
主要方法:
- 建立使用MV和腺相关病毒 (AAV) 进行IGF-1和/或FOXO1过度表达的VIDD大鼠模型.
- 蛋白质和mRNA水平的评估通过西部斑块,ELISA和RT-qPCR.
- 评估腹膜肌的功能,形态,缩,氧化,蛋白质降解,亡和蛋白质分解.
主要成果:
- MV诱导IGF-1下调和FOXO1上调,减少肌肉收缩性和纤维大小.
- MV增加了肌肉缩,氧化和亡的标志物,同时降低了蛋白质合成.
- 过度表达IGF-1扭转了这些效应,而FOXO1.1的共同过度表达则破坏了这些效应.
结论:
- IGF-1保护隔膜肌肉免受VIDD诱导的损伤和功能障碍.
- 这种保护是由FOXO1的下调调节介导的,抑制肌肉分解并促进重塑.
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