title: Rb1 postconditioning attenuates liver warm ischemia-reperfusion injury through ROS-NO-HIF pathway.
abstract: OBJECTIVE
  Ginsenoside Rb1 could prevent ischemic neuronal death and focal cerebral ischemia, but its roles to liver warm I/R injury remain to be defined. We determined if Rb1 would attenuate warm I/R injury in mice.
  
  
  METHODS
  Mice were divided into sham, I/R, Rb1+I/R (Rb1 postconditioning, 20mg/kg, i.p. after ischemia), sham+L-NAME, I/R+L-NAME, and Rb1+I/R+L-NAME groups using 60min of the liver median and left lateral lobes ischemia. Serum levels of alanine aminotransferase (ALT) were measured and morphology changes of livers were evaluated. Contents of nitric oxide (NO) and nitric oxide synthase (NOS), malondialdehye (MDA) and activity of superoxide dismutase (SOD) were measured. Expressions of Akt, p-Akt, iNOS, HIF-1alpha, tumor necrosis factor-a (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) were also determined by western blot or immunohistochemistry.
  
  
  RESULTS
  Rb1 postconditioning attenuated the dramatically functional and morphological injuries. The levels of ALT were significantly reduced in Rb1 group (p<0.05). Rb1 upregulated the concentrations of NO, iNOS in serum, iNOS, and activity of SOD in hepatic tissues (p<0.05), while it dramatically reduced the concentration of MDA (p<0.05). Protein expressions of p-Akt, iNOS and HIF-1alpha were markedly enhanced in Rb1 group. Protein and mRNA expressions of TNF-α and ICAM-1 were markedly suppressed by Rb1 (p<0.05).
  
  
  CONCLUSIONS
  We found that Rb1 postconditioning could protect liver from I/R injury by upregulating the content of NO and NOS, and also HIF-1alpha protein expression. These protective effects could be abolished by L-NAME. These findings suggested Rb1 may have the therapeutic potential through ROS-NO-HIF pathway for management of liver warm I/R injury.
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology of Health Ministry of China, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, PR China.
authors.forename: Yingjia
authors.initials: Y
authors.lastname: Guo
authors.forename: Tong
authors.initials: T
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Shengfu
authors.initials: S
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Wan
authors.forename: Dan
authors.initials: D
authors.lastname: Long
authors.forename: Quansheng
authors.initials: Q
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Feng
authors.forename: Youping
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001831:Body Temperature / Q000502:physiology; D004195:Disease Models, Animal; D036145:Ginsenosides / Q000008:administration & dosage / Q000627:therapeutic use*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D007150:Immunohistochemistry; D057775:Ischemic Postconditioning / Q000379:methods*; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009336:Necrosis; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
chemical_list: D036145:Ginsenosides; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; C442759:ginsenoside Rb1; D019331:NG-Nitroarginine Methyl Ester