title: COX-2 inhibition attenuates lung injury induced by skeletal muscle ischemia reperfusion in rats.
abstract: BACKGROUND
  Skeletal muscle ischemia reperfusion accounts for high morbidity and mortality, and cyclooxygenase (COX)-2 is implicated in causing muscle damage. Downregulation of aquaporin-1 (AQP-1) transmembrane protein is implicated in skeletal muscle ischemia reperfusion induced remote lung injury. The expression of COX-2 in lung tissue and the effect of COX-2 inhibition on AQP-1 expression and lung injury during skeletal muscle ischemia reperfusion are not known. We investigated the role of COX-2 in lung injury induced by skeletal muscle ischemia reperfusion in rats and evaluated the effects of NS-398, a specific COX-2 inhibitor.
  
  
  METHODS
  Twenty-four Sprague Dawley rats were randomized into 4 groups: sham group (SM group), sham+NS-398 group (SN group), ischemia reperfusion group (IR group) and ischemia reperfusion+NS-398 group (IN group). Rats in the IR and IN groups were subjected to 3h of bilateral ischemia followed by 6h of reperfusion in hindlimbs, and intravenous NS-398 8 mg/kg was administered in the IN group. In the SM and SN groups, rubber bands were in place without inflation. At the end of reperfusion, myeloperoxidase (MPO) activity, COX-2 and AQP-1 protein expression in lung tissue, PGE2 metabolite (PGEM), tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels in bronchoalveolar lavage (BAL) fluid were assessed. Histological changes in lung and muscle tissues and wet/dry (W/D) ratio were also evaluated.
  
  
  RESULTS
  MPO activity, COX-2 expression, W/D ratio in lung tissue, and PGEM, TNF-α and IL-1β levels in BAL fluid were significantly increased, while AQP-1 protein expression downregulated in the IR group as compared to that in the SM group (P<0.05). These changes were remarkably mitigated in the IN group (P<0.05). NS-398 treatment also alleviated histological signs of lung and skeletal muscle injury.
  
  
  CONCLUSIONS
  COX-2 protein expression was upregulated in lung tissue in response to skeletal muscle ischemia reperfusion. COX-2 inhibition may modulate pulmonary AQP-1 expression and attenuate lung injury.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, People's Republic of China. Electronic address: arerong1984@126.com.
authors.forename: Liangrong
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, People's Republic of China. Electronic address: 420512181@qq.com.
authors.forename: Yuanlu
authors.initials: Y
authors.lastname: Shan
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, People's Republic of China. Electronic address: 287756120@qq.com.
authors.forename: Yuzhu
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, People's Republic of China. Electronic address: manuscriptjinlida@163.com.
authors.forename: Lida
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, People's Republic of China. Electronic address: the_7_heaven@163.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhuo
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, People's Republic of China. Electronic address: flllgend@qq.com.
authors.forename: Xiangqing
authors.initials: X
authors.lastname: Xiong
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, People's Republic of China. Electronic address: 40590737@qq.com.
authors.forename: Xiyue
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, People's Republic of China. Electronic address: wzlinlina@tom.com.
authors.forename: Lina
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, People's Republic of China. Electronic address: wzyxyfsyy@163.com.
authors.forename: JianXia
authors.initials: J
authors.lastname: Miao
mesh_terms: D000818:Animals; D051398:Aquaporin 1 / Q000235:genetics / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000188:drug therapy*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology; D009578:Nitrobenzenes / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D013449:Sulfonamides / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D053583:Interleukin-1beta; D009578:Nitrobenzenes; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051398:Aquaporin 1; D009195:Peroxidase; D051546:Cyclooxygenase 2
keywords: Aquaporin; Cyclooxygenase; Lung injury; Reperfusion injury; Skeletal muscle