{"title":"SR9009 Regulates Acute Lung Injury in Mice Induced by Sepsis.","authors":"Ming Hu, Li Zhang, Jie Cao, Yu Jiang, Gang Liu","doi":"10.1155/2022/5802938","DOIUrl":null,"url":null,"abstract":"<p><p>Rev-Erb<i>α</i> 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<i>α</i> in acute lung injury (ALI) remain unclarified. Hence, the effect of Rev-Erb<i>α</i> 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-<i>α</i>), 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<i>α</i> via SR9009 attenuates the LPS-induced inflammatory response by suppressing TLR4-regulated NF-<i>κ</i>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 PaCO<sub>2</sub> and increasing arterial PaO<sub>2</sub>, SO<sub>2</sub>, HCO<sub>3</sub> <sup>-</sup>, lactic acid concentration, and blood PH. These findings confirm that SR9009 treatment can alleviate the sepsis-induced lung injury and targeting Rev-Erb<i>α</i> may represent a promising approach for the prevention and management of ALI.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"5802938"},"PeriodicalIF":4.6000,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9270156/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1155/2022/5802938","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
引用次数: 0
Abstract
Rev-Erbα 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-Erbα in acute lung injury (ALI) remain unclarified. Hence, the effect of Rev-Erbα 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-α), 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-Erbα via SR9009 attenuates the LPS-induced inflammatory response by suppressing TLR4-regulated NF-κB 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-Erbα may represent a promising approach for the prevention and management of ALI.
期刊介绍:
ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications.
The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.