title: Oleanolic acid attenuates liver ischemia reperfusion injury by HO-1/Sesn2 signaling pathway.
abstract: BACKGROUND
  Ischemia reperfusion injury (IRI) is unavoidable in liver transplantation and hepatectomy. The present study aimed to explore the possible mechanism and the effect of oleanolic acid (OA) in hepatic IRI.
  
  
  METHODS
  Mice were randomly divided into 6 groups based on different treatment. IRI model: The hepatic artery, portal vein, and bile duct to the left and median liver lobes (70% of the liver) were occluded with an atraumatic bulldog clamp for 90 minutes and then the clamp was removed for reperfusion. The mice were sacrificed 6 hours after reperfusion, and blood and liver tissues were collected. Liver injury was evaluated by biochemical and histopathologic examinations. The expressions of Sesn2, PI3K, Akt and heme oxygenase-1 (HO-1) were measured with quantitative real-time RT-PCR and Western blotting.
  
  
  RESULTS
  The serum aminotransferases level and scores of hepatic histology were increased after reperfusion. The increase was attenuated by pretreatment with OA (P<0.01). Compared with the IR group, OA pretreatment significantly up-regulated the expression of Sesn2, PI3K, Akt and HO-1 in IR livers (P<0.05). Administration of zinc protoporphyrin (ZnPP), an inhibitor of HO-1, diminished the OA effect on HO-1 and Sesn2 expressions (P<0.05) and the protective effect of OA on IRI.
  
  
  CONCLUSIONS
  Our results demonstrate that OA can attenuate hepatic IRI. The protective mechanism may be related to the OA-induced HO-1/Sesn2 signaling pathway.
authors.affiliation: Department of Liver Surgery, First Affiliated Hospital of Nanjing Medical University; Key Laboratory of Living Donor Liver Transplantation of Ministry of Public Health, Nanjing 210029, China. zhangfeng1958@hotmail.com.
authors.forename: Bao-Bin
authors.initials: BB
authors.lastname: Hao
authors.forename: Xiong-Xiong
authors.initials: XX
authors.lastname: Pan
authors.forename: Ye
authors.initials: Y
authors.lastname: Fan
authors.forename: Ling
authors.initials: L
authors.lastname: Lu
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Qian
authors.forename: Xue-Hao
authors.initials: XH
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Rao
mesh_terms: D000818:Animals; D019610:Cytoprotection; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008107:Liver Diseases / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009828:Oleanolic Acid / Q000494:pharmacology*; D010544:Peroxidases; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology; D015427:Reperfusion Injury / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D000084622:Sestrins
chemical_list: D004791:Enzyme Inhibitors; D051547:Heme Oxygenase-1; D008565:Membrane Proteins; D009687:Nuclear Proteins; D009828:Oleanolic Acid; D010544:Peroxidases; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D011524:Protoporphyrins; C017803:zinc protoporphyrin; C529380:Sesn2 protein, mouse; D000084622:Sestrins; C496542:Hmox1 protein, mouse