title: Alpha7 nicotinic acetylcholine receptor activation attenuated intestine-derived acute lung injury.
abstract: BACKGROUND
  Intestinal ischemia-reperfusion (IIR) could lead to acute lung injury, associated with severe alveolar epithelial cells inflammatory and oxidative injury. Alpha7 nicotinic acetylcholine receptor (α7nAChR) is an essential component of the cholinergic anti-inflammatory pathway. The aim of this study was to investigate the important role of α7nAChR on the lung subjected to IIR.
  
  
  METHODS
  Thirty-two Sprague-Dawley rats were randomly divided into four groups (n = 8 in each): sham group (group S), model group (group M), α7nAChR agonist PNU-282987-treated group (group PNU), and specific α7nAChR antagonist methyllycaconitine-treated group (group MLA). Intestinal IR damage was induced by clamping the superior mesenteric artery for 75 min, followed by a 120-min reperfusion. All rats were killed at 2 h after release of the clamps. The histologic examination of lungs was made, and lung water content was detected. Expression levels of malondialdehyde, tumor necrosis factor alpha, interleukin-6, and superoxide dismutase activity of the lungs were detected. Additionally, expression level of toll-like receptor (TLR)4 and nuclear factor-kappaB (NF-κB p65) in the nucleus of lung tissue and apoptosis-related protein (Bax, Bcl-2, and cleaved-caspase3) were detected using Western blot.
  
  
  RESULTS
  Lungs were damaged after intestine IR, manifested by higher lung water content, histologic score, concentrations of interleukin-6, tumor necrosis factor alpha, and malondialdehyde of group M than those of group S, accompanied with decreased superoxide dismutase activity (P < 0.05). PNU treatment could significantly improve the pulmonary function of rats subjected to IIR. These effects of activation of α7nAChR were associated with suppression of TLR4/NF-κB pathway and subsequent reduction of apoptosis-related protein. However, MLA treatment aggravated lung injury.
  
  
  CONCLUSIONS
  α7nAChR plays a role in acute lung injury induced by IIR via attenuating lung oxidative stress and inflammation through suppression of TLR4/NF-κB pathway, resulting in reduction of apoptosis in the lung.
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Emergency, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Ye
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Henan Provincal People's Hospital, Zhengzhou, China.
authors.forename: Guo-Song
authors.initials: GS
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. Electronic address: yaoweifeng881205@163.com.
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Yao
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. Electronic address: 18922102871@163.com.
authors.forename: Gang-Jian
authors.initials: GJ
authors.lastname: Luo
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D007422:Intestines / Q000098:blood supply*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications*; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists*
chemical_list: D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D016328:NF-kappa B; C498513:PNU-282987; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D064569:alpha7 Nicotinic Acetylcholine Receptor
keywords: Acute lung injury; Apoptosis; Intestinal ischemia–reperfusion; TLR4/NF-κB; α7nAChR