| Project/Area Number |
01480223
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | University of Tokyo |
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Principal Investigator |
FUJIWARA Kenji University of Tokyo, Faculty of Medicine, Lecturer., 医学部・附属病院, 講師 (80101088)
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| Co-Investigator(Kenkyū-buntansha) |
持田 智 東京大学, 医学部・附属病院, 医員 (20219968)
富谷 智明 東京大学, 医学部・附属病院, 医員 (90227637)
名越 澄子 東京大学, 医学部・附属病院, 医員
平田 啓一 東京大学, 医学部・附属病院, 医員 (50199064)
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| Project Period (FY) |
1989 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1990: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1989: ¥5,300,000 (Direct Cost: ¥5,300,000)
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| Keywords | fulminant hepatitis / liver regeneration / intravascular coagulation / macrophage / ornithine decarboxylase / plasma membrane / cultured hepatocyte / polyamine / ポリアミン代謝 / オルニシン脱炭酵素 / 分子生物学 / 肝再生促進因子 |
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| Research Abstract |
The aim of this project is to find factors associated with insufficient liver regeneration in fulminant hepatic failure. The following results have been obtained.
1) In massive hepatic necrosis induced in rats by a hepatotoxin, fibrin deposition in the hepatic sinusoids was seen in association with endothelial cell destruction. Such massive hepatic necrosis was also observed when rats received endotoxin following hepatic macrophage activation by administration of killed Corynebacterium parvum or after partial hepatectomy.
2) When rats received putrescine essential for liver regeneration following partial hepatectomy, hepatic DNA synthesis was enhanced with increased hepatic putrescine content, Insulin. glucagon or epidermal growth factor increased hepatic putrescine content through enhancing mRNA content and/or altering posttranscriptional regulation of ornithine decarboxylase, the key enzyme of polyamine production, thus suggesting that polyamine metabolism in the liver after partial hepatectomy may provide a useful tool for evaluation of action sites of hepatotrophic factors.
3) Rat plasma membrane was found to have both stimulatory and inhibitory factors for DNA synthesis by rat hepatocytes in primary culture in the presence of epidermal growth factor or hepatocytes growth factor. The stimulatory factor seemed to be protein in character.
4) In rats with massive hepatic necrosis secondary to fibrin deposition in the hepatic sinusoids, prothrombin time was negatively correlated with hepatic DNA synthesis. The necrosis was attenuated by treatment with anticoagulant infusion. When plasma membrane was obtained from rats given a hepatotoxin, its stimulatory potential for liver proliferation almost disappeared. Circulatory disturbance in the liver and loss of such stimulatory potential of liver plasma membrane may contribute to insufficient liver regeneration in fulminant hepatic failure.
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