›› 2012, Vol. 32 ›› Issue (5): 543-.doi: 10.3969/j.issn.1674-8115.2012.05.003

• Original article (Basic research) • Previous Articles     Next Articles

Expression of urotensin Ⅱ and its relationship with pro-inflammatory cytokines of TNF-alpha and IL-1beta in early stage of acute liver failure

ZHAO Liang, LIANG Dong-yu, LIU Liang-ming, YU Fang-ping, YE Chang-gen   

  1. Department of Hepatology, Shanghai Songjiang District Central Hospital Affiliated to Nanjing Medical University, Songjiang Branch of the First People's Hospital, Shanghai Jiaotong University, Shanghai 201600, China
  • Online:2012-05-28 Published:2012-06-01
  • Supported by:

    National Natural Science Foundation of China, 81070357, 30660066

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Abstract:

Objective To investigate the alteration of expression and secretion of urotensinⅡ(UⅡ) and its effect on pro-inflammatory cytokines in early stage of acute liver failure (ALF) in mice. Methods Sixty male BALB/c mice aged 6 weeks were randomly divided into model group and pre-treatment group, with 30 mice in each group. ALF animal models were established in model group by challenging with 50 μg/kg lipopolysaccharide (LPS) and 800 mg/kg D-galactosamine (D-GalN)(LPS/D-GalN) via intraperitoneal injection, and mice in pre-treatment group were administered with 0.6 mg/kg urantide (UⅡ receptor antagonist) via caudal vein injection 0.5 h before injection of LPS/D-GalN. Mice in both groups were sacrificed 0 h, 0.5 h, 1 h, 2 h and 6 h (6 mice at each time point in each group) after injection of LPS/D-GalN, with those sacrificed 0 h after injection as controls (intraperitoneal injection of 0.2 mL normal saline), and the samples of serum and liver tissues were taken. The expression of UⅡ, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) mRNA and protein was detected by RT-PCR and ELISA respectively.ResultsThe expression and secretion of UⅡ in serum and liver tissues rapidly increased and reached the peak 0.5 h after injection of LPS/D-GalN, lasted till 2 h after injection, decreased 6 h after injection, while still higher than the normal levels 6 h after injection (P<0.05). The level of TNF-α did not significantly increase 0.5 h after injection of LPS/DGalN (P>0.05), reached the peak 1 h after injection (P<0.05), and began to decrease 6 h after injection (P<0.05). The expression and secretion of IL1β did not significantly increase until 6 h after injection of LPS/D-GalN (P<0.05). The application of urantide significantly inhibited the increased expression of UⅡ and expression and secretion of TNF-α and IL-1β induced by LPS/D-GalN challenge (P<0.05). Conclusion UⅡ can stimulate the expression of TNF-α, and may play a key role in the pathogenesis and priming of ALF as a trigger of inflammatory cascade.

Key words: acute hepatic failure, urotensinⅡ, tumor necrosis factor-α, interleukin-1β, mouse