title: Effect of penehyclidine hydrochloride on expressions of MAPK in mice with CLP-induced acute lung injury.
abstract: Penehyclidine hydrochloride (PHC) is a new anticholinergic drug. PHC has been shown to have a good curative effect for sepsis. Mitogen-activated protein kinase (MAPK) has recently been considered to play an important role in sepsis. In this study, the role of MAPK signal pathways in protective effects of PHC preconditioning on acute lung injury in cecal ligation and puncture (CLP)-induced sepsis was investigated. Healthy female mice were randomly divided into 4 groups: sham control, CLP, and 0.3 or 0.45 mg/kg PHC. At 12 h after surgery, arterial blood was drawn for blood gas analysis, and lung tissue samples were collected to examine pulmonary microvascular permeability, IL-6 levels and myeloperoxidase (MPO) activity. MAPK protein expressions were measured using western blot technique. Compared with sham control mice, acute lung injury was induced in CLP group, which was indicated by decreased PaO(2)/FiO(2), increased pulmonary microvascular permeability, IL-6 levels and MPO activity. Furthermore, mice' exposure to CLP induced the increased protein levels of MAPK. Treatment of 0.45 mg/kg PHC markedly improved PaO(2)/FiO(2), decreased pulmonary microvascular permeability, IL-6 levels and MPO activity, and inhibited expressions of extracellular signal-regulated kinase (ERK1/2) and p38 MAPK. Taken together, these results suggest that PHC ameliorated acute lung injury through the inhibition of extracellular signal-regulated kinase (ERK1/2) and p38 MAPK activation in septic mice.
authors.affiliation: Department of Anesthesiology, Zhongnan Hospital of Wuhan University, East-lake Road 169, Wuhan, 430071 Hubei, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhan
authors.forename: Yongpan
authors.initials: Y
authors.lastname: Liu
authors.forename: Zongze
authors.initials: Z
authors.lastname: Zhang
authors.forename: Chang
authors.initials: C
authors.lastname: Chen
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Wang
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002432:Cecum / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D015850:Interleukin-6 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008026:Ligation; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D051379:Mice; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011677:Punctures; D011812:Quinuclidines / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D011812:Quinuclidines; C486140:penehyclidine; D009195:Peroxidase; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D010100:Oxygen