title: Dexmedetomidine attenuates remote lung injury induced by renal ischemia-reperfusion in mice.
abstract: BACKGROUND
  Renal ischemia-reperfusion (I/R) may cause acute lung injury (ALI). The mortality of combined acute kidney injury and ALI is extremely high. Dexmedetomidine, an α(2) adrenergic agonist, exerts potent anti-inflammatory and organoprotective effects in addition to its sedative and analgesic properties. We sought to elucidate whether dexmedetomidine can attenuate lung injury following renal I/R in a murine model of renal I/R.
  
  
  METHODS
  Adult C57BL/6J male mice were randomized to five groups: sham-operated control (Sham); renal I/R (I/R); intraperitoneal injection of dexmedetomidine 25 μg/kg before ischemia (pre-dex) and after perfusion (post-dex); combination of α(2) adrenergic antagonist atipamezole 250 μg/kg prior to dexmedetomidine pre-treatment (atip-dex). Kidney I/R was induced by bilateral renal pedicle clamping for 45 min and followed by 6 h reperfusion. The pulmonary tissues were harvested for histopathological evaluation, wet/dry ratio measurement, biochemical analysis of myeloperoxidase (MPO), Polymerase chain reaction (PCR) determination of Inter-cellular adhesion molecule (ICAM-1) and Tumor necrosis factor - alpha (TNF-α) mRNA.
  
  
  RESULTS
  Renal IR induced significant pulmonary injuries, increased wet/dry ratio together with the enhanced of MPO activities and increased ICAM-1 and TNF-α mRNA level. Both pre- and post-treatment with dexmedetomidine markedly reduced lung edema and inflammatory response and lowered MPO activity and ICAM-1 and TNF-α mRNA expression. The protective effects of dexmedetomidine in the lung were partially reversed by atipamezole, but there were no effect on ICAM-1 and TNF-α mRNA expression level.
  
  
  CONCLUSIONS
  Dexmedetomidine is capable of attenuating remote lung injury induced by renal IR via both α(2) adrenoceptors dependent and independent mechanisms.
authors.affiliation: Department of Pharmacy, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: J
authors.initials: J
authors.lastname: Gu
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: P
authors.initials: P
authors.lastname: Xia
authors.forename: G
authors.initials: G
authors.lastname: Tao
authors.forename: H
authors.initials: H
authors.lastname: Zhao
authors.forename: D
authors.initials: D
authors.lastname: Ma
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003864:Depression, Chemical; D020927:Dexmedetomidine / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D007093:Imidazoles / Q000494:pharmacology; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007674:Kidney Diseases / Q000150:complications*; D055370:Lung Injury / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000502:physiology; D016612:Paraffin Embedding; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000150:complications*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D014409:Tumor Necrosis Factor-alpha; C050701:atipamezole; D018799:Intercellular Adhesion Molecule-1; D020927:Dexmedetomidine; D009195:Peroxidase