title: [Protective effect of minocycline on hepatic ischemia-reperfusion injury in rats].
abstract: OBJECTIVE
  To explore the protective eff ect of minocycline on hepatic ischemia-reperfusion injury (IRI) in rats and the underlying mechanisms.
  
  
  METHODS
  A total of 54 male Sprague-Dawley rats were randomly divided into 3 groups: the sham-operated group (control group), the ischemic-reperfusion (IR group), and the minocycline preconditioning group (n=18 per group). The rats in the minocycline preconditioning group were given minocycline (45 mg/kg) by gastric irrigation at 36 h before operation and then were subsequently administered with minocycline (22.5 mg/kg) at every 12 h. Th e rats were sacrifi ced at 2, 6, 24 h after reperfusion. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were measured. HE staining of liver tissues was performed to detect the histological changes, and the degree of liver IRI according to Suzuki score were calculated. The levels of malondialdehyde (MDA) and myeloperoxidase (MPO) were determined by spectrophotometer; the mRNA expression of tumor necrosis factor-α (TNF-α) and interleukin-1 beta (IL-1β) in the liver were measured by real-time PCR; Dickkopf-1 (DKK-1) and beta-catenin (β-catenin) protein expression in the liver were detected by Western blot.
  
  
  RESULTS
  After 2, 6, 24 h reperfusion, compared with the IR group, the liver function (ALT, AST and LDH) in the minocycline group was significantly improved (all P<0.05); the Suzuki's scores and the levels of hepatic TNF-α and IL-1β mRNA were significantly decreased (all P<0. 05); the MDA and MPO levels the liver were decreased (both P<0.05); the protein expression of hepatic DKK-1 was decreased (P<0.05), while the protein expression of β-catenin was increased (P<0.05).
  
  
  CONCLUSIONS
  Minocycline can alleviate the ischemic-reperfusion injury mainly through reducing oxidative stress and inhibiting the release of pro-inflammatory cytokines depends on the activation of the Wnt/β-catenin signaling pathway in the liver.
authors.affiliation: Organ Transplantation Center, Second Xiangya Hospital, Central South University, Changsha 410011, China.
authors.forename: Yining
authors.initials: Y
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Haizhi
authors.initials: H
authors.lastname: Qi
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D019194:Ischemic Preconditioning; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008911:Minocycline / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: C531384:Dkk1 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D051176:beta Catenin; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D008911:Minocycline