title: Propofol attenuated liver transplantation-induced acute lung injury via connexin43 gap junction inhibition.
abstract: Postoperative acute lung injury (ALI) is a severe complication after liver transplantation, which influences patient survival rate obviously. However, its mechanisms are unclear and effective therapies are still lacking. The current study focused on effects of propofol on liver transplantation-induced ALI and whether its underlying mechanism was relative with connexin43 (Cx43) alternation. The authors postulated that endotoxin induced enhancement of Cx43 gap junction (GJ) plays a critical role in mediating post liver transplantation ALI and that pretreatment with the anesthetic propofol, known to inhibit gap junction, can confer effective protection.
  
  
  
  Male Sprague-Dawley rats underwent autologous orthotopic liver transplantation (AOLT) in the absence or presence of treatments with the selective Cx43 inhibitor, enanthol (0.1 mg/kg) and propofol (50 mg/kg), a commonly used anesthetic in clinical anesthesia. In vitro study, BEAS-2B cells, a kind of lung epithelial cell line expressing Cx43, exposed to lipopolysaccharide (LPS), which mainly contributed to ALI. Function of Cx43 GJ was regulated by Cx43 specific inhibitors, gap26 (300 μM) or enhancer, retinoic acid (10 μM) and two specific siRNAs.
  
  
  
  Compared with the sham group, AOLT results in ALI obviously with plasma endotoxin increase. Cx43 inhibition decreased ALI through inflammatory reaction reduction. In vitro studies, LPS-induced BEAS-2B cells damage was attenuated by Cx43 function inhibition, but amplified by enhancement. Another important finding was propofol reduced Cx43 function and protected against LPS-mediated BEAS-2B cells damage or AOLT-induced ALI, mechanisms of which were also associated with inflammatory reaction decrease.
  
  
  
  Cx43 plays a vital role in liver transplantation-induced ALI. Propofol decreased Cx43 function and protected against ALI in vivo and in vitro. This finding provide a new basis for targeted intervention of organ protection in liver transplantation, even in other kinds of operations.
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road, Guangzhou, People's Republic of China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Yuan
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road, Guangzhou, People's Republic of China.
authors.forename: Guangjie
authors.initials: G
authors.lastname: Su
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road, Guangzhou, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road, Guangzhou, People's Republic of China.
authors.forename: Xinjin
authors.initials: X
authors.lastname: Chi
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road, Guangzhou, People's Republic of China.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road, Guangzhou, People's Republic of China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road, Guangzhou, People's Republic of China. gzcaijun@hotmail.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road, Guangzhou, People's Republic of China. 18922102871@163.com.
authors.forename: Gangjian
authors.initials: G
authors.lastname: Luo
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road, Guangzhou, People's Republic of China. heiziqing@hotmail.com.
authors.forename: Ziqing
authors.initials: Z
authors.lastname: Hei
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology*; D000818:Animals; D002460:Cell Line; D018031:Connexin 43 / Q000378:metabolism*; D017630:Connexins / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D008070:Lipopolysaccharides; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D015742:Propofol / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D014182:Transplantation, Autologous; D000097002:Gap Junction beta-1 Protein
chemical_list: D018031:Connexin 43; D017630:Connexins; D008070:Lipopolysaccharides; D015742:Propofol; D034741:RNA, Small Interfering; D000097002:Gap Junction beta-1 Protein
keywords: Acute lung injury; Connexin43; Liver transplantation; Propofol