文献类型：期刊文献

英文题名：The involvement of oxidative stress and the TLR4/NF-κB/NLRP3 pathway in acute lung injury induced by high-altitude hypoxia

作者：Cao, Wangjie[1,2,3];Zeng, Yuanding[1,2,3];Su, Yun[1,2,3];Gong, Hongxia[1,2,3];He, Jianzheng[1,2,3];Liu, Yongqi[1,2,3];Li, Congyi[1,2,3]

第一作者：曹旺杰;Cao, Wangjie

通信作者：Su, Y[1]

机构：[1]Gansu Univ Tradit Chinese Med, Sch Basic Med, Lanzhou 730000, Peoples R China;[2]Gansu Univ Chinese Med, Prov Level Key Lab Mol Med Major Dis, Lanzhou 730000, Peoples R China;[3]Key Lab Theoret Phys Gansu Prov & Minist Level, Lanzhou 730000, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Tradit Chinese Med, Sch Basic Med, Lanzhou 730000, Peoples R China.|[10735]甘肃中医药大学;

年份：2024

卷号：229

期号：3

外文期刊名：IMMUNOBIOLOGY

收录：;Scopus(收录号：2-s2.0-85193914259);WOS:【SCI-EXPANDED(收录号:WOS:001246908600001)】；

基金：This work was supported by the Regional Science Fund Project of the National Natural Science Foundation of China (82060833) , Gansu Provincial Science and Technology Program funding (23JRRA1212) , Key Laboratory 2019-2020 Open Fund Project on Researching Chemistry and Quality of Chinese (Tibetan) Medicine in Colleges and Universities of Gansu Province (zzy 2019-06) , as well as Gansu Province College Youth Doctoral Fund (2022QB-102) .

语种：英文

外文关键词：High -altitude hypoxia; Acute lung injury; Oxidative stress; Inflammatory response; TLR4/NF-kappa B/NLRP3 pathway

摘要：Objective: This study investigated the effect of oxidative stress and the TLR4/NF-kappa B/NLRP3 pathway on the pathogenesis of acute lung injury (ALI) induced by high-altitude hypoxia. Methods: Rats were placed in an animal hyperbaric oxygen chamber to establish a rat model of ALI induced by high-altitude hypoxia after treatment with N-acetylcysteine (NAC; a reactive oxygen species [ROS] inhibitor) or/and MCC950 (an NLPR3 inflammasome inhibitor). After modeling, the wet-to-dry weight ratio (W/D) of rat lung tissues was calculated. In lung tissues, ROS levels were detected with immunofluorescence, the enzyme activity was tested with the kit, and the expression of TLR4/NF-kappa B/NLRP3 pathway-related genes and proteins was measured with western blotting and qRT-PCR. The levels of inflammatory factors in the serum were quantified with ELISA. Results: After modeling, rats showed significantly increased W/D, ROS levels, and Malondialdehyde (MDA) concentrations and markedly diminished Superoxide dismutase (SOD) and Glutathione (GSH) concentrations in lung tissues (all P < 0.01), accompanied by substantially enhanced serum levels of TNF-alpha, IL-6, and IL-1 beta, significantly reduced serum levels of IL-10, and remarkably augmented TLR4, NLRP3, p-NF-kappa B p65, NF-kappa B p65 mRNA, and Caspase-1 expression in lung tissues (all P < 0.01). Furthermore, treatment with NAC or MCC950 alone or in combination prominently lowered the W/D of lung tissues (P < 0.01), serum levels of TNF-alpha (P < 0.05), IL-6 (P < 0.05), and IL-1 beta (P < 0.01), and NF-kappa B p65 expression and phosphorylation (P < 0.05, P < 0.01) while significantly increasing SOD and GSH concentrations (P < 0.05, P < 0.01) and serum levels of IL-10 (P < 0.01) in modeled rats. Meanwhile, treatment of NAC alone or combined with MCC950 significantly reduced MDA concentration and ROS levels (P < 0.05, P < 0.01) in modeled rats, and treatment of MCC950 alone or combined with NAC considerably declined TLR4, NLRP3, and Caspase-1 expression in modeled rats (P < 0.05, P < 0.01). Conclusion: Inhibition of oxidative stress and the TLR4/NF-kappa B/NLRP3 pathway can ameliorate ALI in rats exposed to high-altitude hypoxia.