• L-M Liu, J-X Zhang, X-P Wang, H-X Guo, H Deng, and J Luo.
• Jiangxi Provincial Key Laboratory of Molecular Medicine, Nanchang, China.
• Eur. J. Clin. Invest. 2010 Feb 1; 40 (2): 127-38.

BackgroundFulminant hepatic failure (FHF) has a high mortality resulted from massive hepatic apoptosis and haemorrhage necrosis; it is required to develop a valid therapy directed towards hepatocyte protection and regeneration. Pim-3, a hepatic growth stimulator, belongs to the serine/threonine kinase Pim-family that has been implicated in gp130-mediated induction of cell proliferation, protection from apoptosis downstream of Signal transducer and activator of transcription 3 (STAT3) and vascular endothelial growth factor-A-dependent vasculogenesis and angiogenesis, thus is suggested to possibly play a role in the tissue repair of FHF.Materials And MethodsMale Wistar rats received simultaneous intraperitoneal injections of lipopolysaccharide (LPS) (100 microg kg(-1)) and D-galactosamine (D-GalN) (600 mg kg(-1)). One day prior to LPS/D-GalN administration, naked plasmid or Ringer's solution was injected via tail vein by hydrodynamics-based procedure.ResultsExogenous Pim-3 gene protected against LPS/D-GalN-induced lethality with survival rate of more than 80% and improved the hepatic pathomorphism. The fractions of hepatic apoptotic-positive cells and the levels of caspase-3 activity were markedly lower in Pim-3-pretreated rats. Furthermore, exogenous Pim-3 significantly inhibited expression of tumour necrosis factor-alpha and interleukin-1beta in the liver, declined p53 and inducible nitric oxide synthase mRNAs levels, but elevated levels of Bcl-2 protein, an anti-apoptosis member of Bcl-2 family, in the liver. Exogenous Pim-3, however, showed little effect on expression of Bax, a pro-apoptosis member of Bcl-2 family.ConclusionsPim-3 gene could protect rats from FHF by inhibiting liver apoptosis and improving inflammatory response of liver tissues, which could be associated with inhibiting expression of inflammatory mediators and promoting expression of anti-apoptosis protein Bcl-2.

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