title: Pre-treatment with isoflurane ameliorates renal ischemic-reperfusion injury in mice.
abstract: OBJECTIVE
  Perioperative renal dysfunction is associated with a high mortality. The aim of this study was to investigate whether isoflurane preconditioning provides a protection against renal ischemic-reperfusion injury and whether hypoxia inducible factor 1 α (HIF-1 α) is responsible for the protection afforded by isoflurane in mice.
  
  
  METHODS
  Adult male C57BL/6 mice received vehicle (PBS), scrambled siRNA or HIF-1 α siRNA via hydrodynamic injection through tail vein. Twenty-four hours after injection, they were exposed to 1.5% isoflurane in oxygen enriched air for 2h while controls without injection were exposed to oxygen enriched air. Twenty-four hours after gas exposure, mice were sacrificed and their kidney were harvested for western blot while other cohorts underwent renal ischemia-reperfusion injury induced by bilateral renal pedicle clamping for 25 min for renal histological or functional analysis 24h after reperfusion or by unilateral clamping for 40 min for survival rate analysis.
  
  
  RESULTS
  Survival rate and the expression of HIF-1 α and erythropoietin were significantly increased while apoptosis, renal tubule score, blood plasma creatinine and urea were decreased by isoflurane preconditioning. HIF-1 α siRNA but not scrambled siRNA injection abrogated the protective effect of isoflurane preconditioning.
  
  
  CONCLUSIONS
  Our data suggested that isoflurane preconditioning provided a protection against renal ischemic-reperfusion injury which is very likely due to hypoxia inducible factor-1 α upregulation.
authors.affiliation: Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Han
authors.initials: H
authors.lastname: Huang
authors.forename: Jian
authors.initials: J
authors.lastname: Cheng
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.forename: Hailin
authors.initials: H
authors.lastname: Zhao
authors.forename: Marcela P
authors.initials: MP
authors.lastname: Vizcaychipi
authors.forename: Daqing
authors.initials: D
authors.lastname: Ma
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000096:biosynthesis; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D020287:In Situ Nick-End Labeling; D007530:Isoflurane / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D034741:RNA, Small Interfering / Q000235:genetics; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors; D014508:Urea / Q000097:blood
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020011:Protective Agents; D034741:RNA, Small Interfering; D004921:Erythropoietin; D014508:Urea; D003404:Creatinine; D007530:Isoflurane