title: Dexmedetomidine ameliorates acute lung injury following orthotopic autologous liver transplantation in rats probably by inhibiting Toll-like receptor 4-nuclear factor kappa B signaling.
abstract: BACKGROUND
  To investigate whether pretreatment with dexmedetomidine (Dex) has a protective effect against acute lung injury (ALI) in an orthotopic autologous liver transplantation (OALT) rat model and to explore the mechanisms responsible for the protective effect of Dex against lung injury.
  
  
  METHODS
  Forty-eight rats underwent OALT and were randomly divided into six groups (n = 8 in each group) that received 10 µg/kg Dex, 50 µg/kg Dex, 50 µg/kg Dex + nonspecific α2-adrenergic receptor (AR) antagonist atipamezole, 50 µg/kg Dex + specific α2B/C-AR antagonist ARC-239, 50 µg/kg Dex + specific α2A-AR antagonist BRL-44408, or the same amount of normal saline. The sham rats (n = 8) underwent anesthesia induction, laparotomy, and separation of the portal vein without liver ischemia and reperfusion. Lung tissue sections were stained with hematoxylin and eosin (HE) to visualize the damage. The expression of Toll-like receptor 4 (TLR4) and the phospho-nuclear factor (NF)-κB p65 subunit as well as inflammatory cytokines was measured.
  
  
  RESULTS
  Rats exhibited increased histological lung injury scores and pulmonary edema following OALT. Pretreatment with 50 μg/kg Dex attenuated OALT-induced lung injury in rats, probably by inhibiting the activation of the TLR4-NF-κB signaling pathway. The protective effect of Dex could be blocked by atipamezole or BRL-44408, but not by ARC-239, suggesting these effects of Dex were mediated, at least in part, by the α2A-AR.
  
  
  CONCLUSIONS
  Dex exerts protective effects against ALI following OALT, and this protection is associated with the suppression of TLR4-NF-κB signaling. Thus, pretreatment with Dex may be a useful method for reducing lung damage caused by liver transplantation.
authors.affiliation: Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510630, China. chixinjin@yeah.net.
authors.forename: Xinjin
authors.initials: X
authors.lastname: Chi
authors.affiliation: Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510630, China. 150983404@qq.com.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510630, China. wmrgwl@21cn.com.
authors.forename: Wanling
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510630, China. gjq1973@163.com.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Guan
authors.affiliation: Department of Anesthesiology, Fujian Provincial Hospital, Fuzhou, Fujian, 350001, China. 505315964@qq.com.
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital, University of South China, Hengyang, Hunan, 421001, China. 772757499@qq.com.
authors.forename: Yiheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Thyroid and Breast Surgery, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510630, China. drlixi@gmail.com.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510630, China. cj_gz@tom.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D020927:Dexmedetomidine / Q000494:pharmacology / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000378:metabolism; D016031:Liver Transplantation; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D021122:Protein Subunits / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014182:Transplantation, Autologous; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D016328:NF-kappa B; D021122:Protein Subunits; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D020927:Dexmedetomidine; D009195:Peroxidase