title: [Effects of urantide, a urotensin receptor inhibitor, on acute hepatocyte apoptosis in mice].
abstract: OBJECTIVE
  To explore the effects of urantide, a urotensin II receptor (UT) inhibitor, on lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute hepatocyte apoptosis in mice.
  
  
  METHODS
  Male BALB/c mice were randomly divided into 4 groups (n = 6 each): normal control, pre-treatment control, model and pre-treatment model. The pre-treatment control and pre-treatment model groups received urantide (0.6 mg/kg body weight) by a caudal vein injection. At 30 minutes post-injection, the model and pre-treatment model groups were treated with LPS/D-GalN to induce acute hepatocyte apoptosis via an intraperitoneal injection. Hepatocyte apoptosis was examined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and caspase-3 colorimetric assay. The expressions of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interferon-γ (IFN-γ) and interleukin-1 beta (IL-1β), were detected by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Massive hepatocyte apoptosis were detected in the model group. The apoptotic index was clearly reduced in the pre-treatment model group [(26 ± 11)% vs (77 ± 20)%, P < 0.01]. And the activity of caspase-3 was also lower in the pre-treatment model group than that in the model group [(2.50 ± 0.83) pmol · min(-1) · mg(-1) vs (3.76 ± 0.42) pmol · min(-1) · mg(-1), P < 0.01]. In addition, the serum and liver tissue levels of TNF-α, IL-1β and IFN-γ in the pre-treatment model group were significantly lower than those in the model group[1.69 ± 0.47 vs 3.57 ± 0.79, 0.31 ± 0.02 vs 0.46 ± 0.06, 2.81 ± 0.72 vs 3.35 ± 0.84, (233 ± 36) pg/ml vs (441 ± 157) pg/ml, (228 ± 21) pg/ml vs (364 ± 20) pg/ml, (93.8 ± 5.2) pg/ml vs (180.3 ± 4.3) pg/ml, all P < 0.01].
  
  
  CONCLUSIONS
  LPS/D-GalN-induced acute hepatocyte apoptosis can be inhibited by a pretreatment of urantide through an inhibition of expression and secretion of proinflammatory cytokines. The UII/UT receptor system plays a pivotal role in the liver immuno-inflammatory injury of acute liver failure (ALF). And it may become a new drug target of ALF therapy.
authors.affiliation: Cadres Ward, Shanghai Songjiang Central Hospital Affiliated to Nanjing Medical University, Songjiang Hospital Affiliated to First People's Hospital, Shanghai Jiaotong University, Shanghai 201600, China.
authors.forename: Fang-ping
authors.initials: FP
authors.lastname: Yu
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.forename: Liang-ming
authors.initials: LM
authors.lastname: Liu
authors.forename: Dong-yu
authors.initials: DY
authors.lastname: Liang
authors.forename: Dao-hua
authors.initials: DH
authors.lastname: Yang
authors.forename: Fang-fang
authors.initials: FF
authors.lastname: Zhang
authors.forename: Chang-gen
authors.initials: CG
authors.lastname: Ye
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014579:Urotensins / Q000494:pharmacology*
chemical_list: D053583:Interleukin-1beta; D010446:Peptide Fragments; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha; D014579:Urotensins; C492079:urotensin II (4-11), Pen(5)-Trp(7)-Orn(8)-; C512325:urotensin II receptor, mouse; D007371:Interferon-gamma; C505409:Casp3 protein, mouse; D053148:Caspase 3