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Factors Associated with Insufficient Liver Regeneration in Fulminant Hepatic Failure

暴发性肝衰竭中肝脏再生不足的相关因素

基本信息

批准号：
01480223
负责人：
FUJIWARA Kenji
金额：
$ 4.29万
依托单位：
University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

项目摘要

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.

该项目的目的是寻找与爆发性肝衰竭中肝脏再生不足相关的因素。结果表明：1）在肝毒素诱导的大鼠肝大面积坏死中，肝窦内纤维蛋白沉积与内皮细胞破坏有关。当大鼠在通过施用杀死的短小棒状杆菌激活肝巨噬细胞后或在部分肝切除术后接受内毒素时，也观察到这种大面积肝坏死。2）当大鼠在部分肝切除术后接受对肝再生至关重要的腐胺时，肝DNA合成随着肝腐胺含量、胰岛素的增加而增强。胰高血糖素或表皮生长因子通过增加mRNA含量和/或改变鸟氨酸脱羧酶（多胺产生的关键酶）的转录后调节来增加肝腐胺含量，因此，部分肝切除术后肝脏中的多胺代谢可能为评估肝营养因子的作用位点提供有用的工具。在原代培养的大鼠肝细胞中，在表皮生长因子或肝细胞生长因子的存在下，发现大鼠质膜具有刺激和抑制大鼠肝细胞DNA合成的因子。4）在继发于肝窦纤维蛋白沉积的大面积肝坏死大鼠中，凝血酶原时间与肝DNA合成呈负相关。通过抗凝剂输注治疗可减轻坏死。当从给予肝毒素的大鼠获得质膜时，其对肝增殖的刺激潜力几乎消失。肝循环障碍和肝细胞膜的这种刺激潜力的丧失可能导致暴发性肝功能衰竭时肝再生不足。