title: Alpha7 Nicotine Acetylcholine Receptor Agonist PNU-282987 Attenuates Acute Lung Injury in a Cardiopulmonary Bypass Model in Rats.
abstract: Cardiopulmonary bypass (CPB) carries a risk of lung ischemia-reperfusion, leading to acute lung injury (ALI). Alpha7 nicotinic acetylcholine receptor (alpha7nAChR) has been implicated in the release of high mobility group box1 (HMGB1), which promotes systemic inflammation in response to ischemia-reperfusion injury. However, the specific role of alpha7nAChR in CPB is poorly understood. This study employed the alpha7nAChR agonist PNU-282987 and a rat model of CPB to determine whether alpha7nAChR was associated with CPB-induced lung damage.
  
  
  
  Thirty Sprague-Dawley rats were randomly divided into five groups as follows: normal group, sham group, CPB group, PNU-282987 plus CPB group, and PNU-282987 plus sham group. Rats were subjected to CPB under anesthesia for 60 min. PNU-282987 (4.8 mg/kg) was administered via arterial inflow. Two hours post-CPB, samples of blood, bronchoalveolar lavage fluid (BALF), and lung tissues were processed for investigations.
  
  
  
  In CPB rats, structural damage in the lung was marked. Density of alpha7nAChR of the lung in the CPB group was significantly less than all other groups, while lung edema, inflammatory markers in serum and lung, protein concentrations in BALF were significantly higher. In the PNU-282987 plus CPB group, by all the above measures the CPB-associated effects were significantly ameliorated but were not identical to the control groups.
  
  
  
  Our results suggest that PNU-282987 affords protective effect against CPB-induced ALI, and inhibits HMGB1 release.
authors.affiliation: *Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China †Department of Critical Care Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jiaxi
authors.initials: J
authors.lastname: Ge
authors.forename: Jie
authors.initials: J
authors.lastname: Tian
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Hou
authors.forename: Zhankui
authors.initials: Z
authors.lastname: Wang
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: He
authors.forename: Xiangrui
authors.initials: X
authors.lastname: Wang
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D001549:Benzamides / Q000627:therapeutic use*; D015153:Blotting, Western; D001643:Bridged Bicyclo Compounds / Q000627:therapeutic use*; D002315:Cardiopulmonary Bypass; D004195:Disease Models, Animal; D024243:HMGB1 Protein / Q000378:metabolism; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists / Q000378:metabolism*
chemical_list: D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D024243:HMGB1 Protein; D053583:Interleukin-1beta; C498513:PNU-282987; D014409:Tumor Necrosis Factor-alpha; D064569:alpha7 Nicotinic Acetylcholine Receptor