SR9009 Regulates Acute Lung Injury in Mice Induced by Sepsis

作者全名："Hu, Ming; Zhang, Li; Cao, Jie; Jiang, Yu; Liu, Gang"

作者地址："[Hu, Ming; Zhang, Li; Cao, Jie; Jiang, Yu; Liu, Gang] Chongqing Med Univ, Dept Crit Care Med, Chongqing 400016, Peoples R China"

通信作者："Jiang, Y (通讯作者)，Chongqing Med Univ, Dept Crit Care Med, Chongqing 400016, Peoples R China."

来源：CANADIAN RESPIRATORY JOURNAL

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000825124400001

JCR分区：Q4

影响因子：2.2

年份：2022

卷号：2022

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Rev-Erb alpha is a nuclear heme receptor, transcriptional repressor, and critical component of the molecular clock that drives daily rhythms of metabolism. However, the roles of Rev-Erb alpha in acute lung injury (ALI) remain unclarified. Hence, the effect of Rev-Erb alpha on lung injury of sepsis mice is investigated here. The mice sepsis model is established using lipopolysaccharide (LPS) injection, and the expression levels of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-10 (IL-10) in both RAW246.7 cells and lung tissues, are tested. The inflammatory response is obviously enhanced in LPS-constructed sepsis mice and alleviated by SR9009 agonist treatment. Cell-based experiments reveal that pharmacological activation of Rev-Erb alpha via SR9009 attenuates the LPS-induced inflammatory response by suppressing TLR4-regulated NF-kappa B activation. Sepsis induces the increase in W/D ratio; promotes the levels of malondialdehyde (MDA), lactic acid (LA), and superoxide dismutase (SOD); and inhibits the levels of glutathione (GSH), whereas SR9009 treatment could effectively yield beneficial effects on metabolism. In addition, SR9009 treatment ameliorates acidosis and hypoxemia by efficiently decreasing arterial PaCO2 and increasing arterial PaO2, SO2, HCO3-, lactic acid concentration, and blood PH. These findings confirm that SR9009 treatment can alleviate the sepsis-induced lung injury and targeting Rev-Erb alpha may represent a promising approach for the prevention and management of ALI."

基金机构：National Science Foundation of Chongqing [cstc2020jcyj-msxmX0254]; Chongqing Yuzhong District Science and Technology Planning Project [20170103]

基金资助正文：AcknowledgmentsThis work was supported by the National Science Foundation of Chongqing (No.: cstc2020jcyj-msxmX0254) and Chongqing Yuzhong District Science and Technology Planning Project (No.: 20170103).