title: Post-conditioning with sevoflurane induces heme oxygenase-1 expression via the PI3K/Akt pathway in lipopolysaccharide-induced acute lung injury.
abstract: The aim of the present study was to explore the regulatory mechanism of heme oxygenase-1 (HO-1) expression induced by sevoflurane (Sevo) in lipopolysaccharide (LPS)‑induced acute lung injury (ALI). Sprague-Dawley rats were divided randomly into six groups: (A) Control, (B) 2.4% Sevo only, (C) LY294002 (PI3K inhibitor) only, (D) LPS + 2.4% Sevo, (E) LY294002 + LPS + 2.4% Sevo and (F) LPS only. The pathological changes in wet/dry weight ratio (W/D), the activities of superoxide dismutase, myeloperoxidase (MPO), malondialdehyde, and HO-1, as well as the expression of intercellular adhesion molecule (ICAM-1), HO-1, phospho-phosphatidylinositol 3-kinase (pPI3K) and phospho-Akt (pAkt) were recorded. Sevo post-conditioning was able to effectively protect from ALI with decreasing pathomorphological scores, MPO activity, W/D and the mRNA and protein expression levels of ICAM-1. Sevo promotes HO-1 expression via the PI3K/protein kinase B (PI3K/Akt) pathway with activation of pPI3K and pAkt. Inhibition of the PI3K/Akt pathway by LY294002 partly eliminates the protective effects of Sevo. It is concluded that Sevo post-conditioning has a vital role in inducing the upregulation of HO-1 expression via the PI3K/Akt pathway to alleviate ALI.
authors.affiliation: Department of Critical Care Medicine, Hunan Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Shuangping
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Hunan Provincial Tumor Hospital, Changsha, Hunan 410013, P.R. China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Critical Care Medicine, Hunan Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Lemeng
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Critical Care Medicine, Hunan Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Yuhang
authors.initials: Y
authors.lastname: Ai
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics*; D008070:Lipopolysaccharides / Q000009:adverse effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008738:Methyl Ethers / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D000077149:Sevoflurane; D015398:Signal Transduction / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D008738:Methyl Ethers; D012333:RNA, Messenger; D000077149:Sevoflurane; D008315:Malondialdehyde; D009195:Peroxidase; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt