Zhang Dan, Zhou Jian, Ye Le Chi, Li Jing, Wu Zhenzhou, Li Yuping, Li Chichi
Department of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Wenzhou City, Zhejiang Province, P.R. China.
Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
J Cell Physiol. 2018 Jan;233(1):688-698. doi: 10.1002/jcp.25928. Epub 2017 May 19.
Understanding the role and underlying regulation mechanism of autophagy in lipopolysaccharide-induced lung injury (LPS-LI) may provide potentially new pharmacological targets for treatment of acute lung injury. The aim of this study was to investigate the functional significance of autophagy in LPS-LI. The autophagy of human pulmonary microvascular endothelial cells (HPMVECs) and mice was inhibited before they were challenged with LPS. In vitro, permeability, vitality, and the LDH release rate of the cells were detected, the zonula occluden-1 (ZO-1) expression and the stress fiber formation were determined. In vivo, the lung injury was assessed. We found LPS caused high permeability and increased lactate dehydrogenase (LDH) release rate, lowered viability of the cells, inhibited the ZO-1 expression and induced stress fiber formation, these effects were further aggravated by prohibiting the level of autophagy. Consistently, in in vivo experiments, LPS-induced serious lung injury, which was reflected as edema, leukocyte infiltration and hemorrhage in lung tissue, and the high concentration of pro-inflammation cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β in bronchoalveolar lavage fluid (BALF). Inhibiting autophagy further exacerbated LPS-LI. It appears that autophagy played a protective role in LPS-LI in part through restricting the injury of lung microvascular barrier.
了解自噬在脂多糖诱导的肺损伤（LPS-LI）中的作用及潜在调控机制，可能为急性肺损伤的治疗提供新的潜在药理学靶点。本研究旨在探讨自噬在LPS-LI中的功能意义。在用LPS刺激人肺微血管内皮细胞（HPMVECs）和小鼠之前，抑制其自噬。在体外，检测细胞的通透性、活力和乳酸脱氢酶（LDH）释放率，测定紧密连接蛋白-1（ZO-1）表达和应力纤维形成。在体内，评估肺损伤情况。我们发现LPS导致细胞高通透性和LDH释放率增加，细胞活力降低，抑制ZO-1表达并诱导应力纤维形成，抑制自噬水平会进一步加重这些效应。同样，在体内实验中，LPS诱导严重的肺损伤，表现为肺组织水肿、白细胞浸润和出血，以及支气管肺泡灌洗液（BALF）中促炎细胞因子肿瘤坏死因子（TNF）-α和白细胞介素（IL）-1β浓度升高。抑制自噬进一步加重LPS-LI。自噬似乎部分通过限制肺微血管屏障损伤在LPS-LI中发挥保护作用。
