在SIRT1/GPS2/AIP1轴调节呼吸机引起的肺损伤的肺血管透性
Yi Zhang1,2, Cuicui Cao3,4, Chang Sun2
1Department of Anesthesiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China.
Molecular and cellular biochemistry
|May 21, 2025
概括
机械通风可以损害肺部. 这项研究揭示了SIRT1/GPS2/AIP1通路调节氧化应激和肺屏障完整性,为预防呼吸器诱导的肺损伤 (VILI) 提供了新的见解.
科学领域:
- 肺部医学 肺部医学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 机械呼吸 (MV) 对于生命支持至关重要,但可能导致呼吸器诱导的肺损伤 (VILI).
- VILI涉及到肺内皮屏障完整性的破坏,但潜在的机制仍然不清楚.
- 细胞连接蛋白受到MV的影响,导致屏障功能障碍.
研究的目的:
- 为了研究ASK1相互作用蛋白-1 (AIP1),G蛋白通路抑制剂2 (GPS2) 和sirtuin 1 (SIRT1) 在VILI中的作用.
- 阐明这些蛋白质在机械应力期间调节肺内皮壁完整性的机制.
- 了解SIRT1/GPS2/AIP1轴对氧化应激和细胞结蛋白表达的影响.
主要方法:
- 人类肺微血管内皮细胞 (HLMVECs) 经过AIP1,GPS2和SIRT1.1的siRNA或cDNA转染后经过循环拉伸 (CS).
- 在机械通风之前,C57BL/6N小鼠先用SIRT1 siRNA进行预处理.
- 评估了氧化应激标志物 (ROS),细胞结蛋白水平,细胞因子产生 (IL-6,IL-1β) 和肺.
主要成果:
- 循环拉伸 (20%) 激活了氧化应激,增加了ROS的产生,并破坏了内皮屏障的完整性.
- AIP1的耗尽加剧了ROS产量和屏障破坏.
- GPS2枯竭减少了AIP1和细胞结蛋白,GPS2过度表达逆转了效应.
- 由于SIRT1的减少,GPS2和AIP1的减少,ROS的增加,细胞结蛋白的减少,在小鼠中恶化VILI,细胞因子和的增加.
结论:
- 循环机械拉伸通过氧化应激和改变细胞结 protein 破坏了内皮屏障的完整性.
- 在VILI期间,SIRT1/GPS2/AIP1轴在调节ROS产生和保持肺内皮屏障完整性方面发挥着关键作用.
- 准SIRT1/GPS2/AIP1通路可能是缓解VILI的一种治疗策略.
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