title: Administration of SB239063, a potent p38 MAPK inhibitor, alleviates acute lung injury induced by intestinal ischemia reperfusion in rats associated with AQP4 downregulation.
abstract: Acute lung injury (ALI), induced by intestinal ischemia reperfusion (II/R) injury, is characterized by pulmonary edema and inflammation. Aquaporin 4 (AQP4), has been pointed out recently involving in edema development. Previous studies have shown that p38 mitogen activated protein kinase (MAPK) activation resulted in lung inflammation, while p38 MAPK inhibitor can alleviate the pathology injury of lung tissue. However, the regulated mechanism of p38 MAPK in ALI induced by II/R is unclear. In this study, we established II/R rats' model by clamping the superior mesenteric artery (SMA) and coeliac artery (CA) for 40min and subsequent reperfusion for 16h, 24h, 48h. Subsequently, SB239063, a specific inhibitor of the activity of p38 MAPK, was injected (10mg/kg) intraperitoneally 60min before the operation. The severity of ALI was determined by histology analysis (HE staining and ALI scoring) and lung edema (lung wet/dry weight ratio) assessment. Western blot (WB) was applied to detect the expression level of AQP4 and phosphorylated (P)-p38 MAPK, and the localization of AQP4 was detected by immunofluorescent staining (IF). We found that AQP4 could express in the lung tissue. II/R could significantly induce lung injury, confirmed by lung injury scores and lung wet/dry weight ratios. The level of P-p38 MAPK and AQP4 were largely up-regulated in lung tissues. Moreover, inhibition of p38 MAPK activity could effectively down-regulate AQP4 expression and diminish the severity of II/R-induced ALI. These novel findings suggest that inhibition of p38 MAPK function should be a potential strategy for the prevention or treatment of ALI, by targeting AQP4 in future clinic trial.
authors.affiliation: Department of Respiration, First People's Hospital of Yunnan Province, Kunming, Yunnan 650000, People's Republic of China; Department of Anesthesiology and Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China.
authors.forename: Liu-Lin
authors.initials: LL
authors.lastname: Xiong
authors.affiliation: Department of Respiration, First People's Hospital of Yunnan Province, Kunming, Yunnan 650000, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of Respiration, First People's Hospital of Yunnan Province, Kunming, Yunnan 650000, People's Republic of China.
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Ma
authors.affiliation: Institute of Neuroscience, Kunming Medical University, Kunming 650000, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Dai
authors.affiliation: Department of Histology and Neurobiology, West China School of Basic Medical Science and Forensic Medicine, Sichuan University, Chengdu 610041, People's Republic of China.
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Qin
authors.affiliation: Department of Respiration, First People's Hospital of Yunnan Province, Kunming, Yunnan 650000, People's Republic of China.
authors.forename: Rui-Ai
authors.initials: RA
authors.lastname: Yang
authors.affiliation: Department of Respiration, First People's Hospital of Yunnan Province, Kunming, Yunnan 650000, People's Republic of China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Xu
authors.affiliation: Department of Respiration, First People's Hospital of Yunnan Province, Kunming, Yunnan 650000, People's Republic of China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Department of Respiration, First People's Hospital of Yunnan Province, Kunming, Yunnan 650000, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology and Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China.
authors.forename: Qin-Jie
authors.initials: QJ
authors.lastname: Xia
authors.affiliation: Institute of Neuroscience, Kunming Medical University, Kunming 650000, People's Republic of China; Department of Anesthesiology and Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China. Electronic address: tinghua_neuron@263.net.
authors.forename: Ting-Hua
authors.initials: TH
authors.lastname: Wang
authors.affiliation: Department of Respiration, First People's Hospital of Yunnan Province, Kunming, Yunnan 650000, People's Republic of China. Electronic address: yunhuizhang3188@126.com.
authors.forename: Yun-Hui
authors.initials: YH
authors.lastname: Zhang
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D007422:Intestines / Q000601:surgery; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008638:Mesenteric Arteries / Q000601:surgery; D058990:Molecular Targeted Therapy; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D007093:Imidazoles; D011743:Pyrimidines; D048051:p38 Mitogen-Activated Protein Kinases; C406525:SB 239063
keywords: AQP4; Acute lung injury; Intestinal ischemia-reperfusion; Rat; p38 MAPK