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Human hepatopoietin augmenter of liver regeneration──A hepatotrophic factor for liver regeneration, and its potential antihepatitis effect in vivo

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Chinese Science Bulletin 1998年第12期43卷 1026-1031页

作者： yang xiaoming 1,{1., zhou ping 3. xie ling 1,{3., wu zuze 1 and he fuchu 1 1. institute of radiation medicine, beijing 100850, china 2. No. 252 Hospital of PLA, Baoding 071.00, china 3. General Hospital of the Air institute of {1. medicine Beijing China No. 252 Hospital of PLA Baoding China General Hospital of the Air Force of PLA Beijing China

The effect of human hapatopoietin i.e. augmenter of liver regeneration (hALR) was determined on hepatocyte DNA synthesis, and on CCl 4-induced hepatitis in animal in vitro and in vivo. It is found that ALR could directly stimulate DNA synthesis of hepatocytes in primary culture in a dose-dependent manner. In 3.% hepatectomied rats, significant DNA synthesis occurred in control rats ; even so, exogenous hALR gene encoding protein increased DNA synthesis of regeneration liver by 2.3.fold compared with control rats. A lower dose of CCl 4 was administrated in rats and the effect of ALR on DNA synthesis of regenerating liver 48 h after CCl 4 administration was analyzed. Few Budr-labeled hepatocytes were visible in control rats. However, exogenous hALR markedly increased the number of labeled cells in a dose-dependent manner. Statistical analysis showed that 1. or 40 μg·kg -1.ALR protein stimulated DNA synthesis by 1.7 and 4.8 fold respectively. In addition to enhancing cell growth, adiministration of hALR achieved a significant improvement in reversing the lethality of rat hepatic failure when compared with that of control group; the elevation of cytosolic enzymes was dramatically suppressed by exogenous hALR in CCl 4-treated mice in vivo and in vitro; histologically, hepatocytes around the central vein were necrotic, and the degree of hepatocyte necrosis in control mice was more prominent than that in the mice given 40 μg·kg-1.hALR 48 h after CCl 4 administration. We also noted that hALR had a strong antihepatitis effect in vitro which was determined with primary cultured rat hepatocytes. These findings suggest that hALR protects the integrity of hepatocytes against severe hepatitis, and indicate that ALR may be an important regulator of liver regeneration and play a major role in liver injury repair. It proves ALR adminstration to be a useful treatment to accelerate liver regeneration and to prevent the onset of hepatitis or intrahepatic cholestasis induced by toxin.

关键词： liver regeneration hepatopoietin DNA synthesis hepatitis.

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