Factors Associated with Insufficient Liver Regeneration in Fulminant Hepatic Failure

该项目的目的是找出暴发性肝衰竭患者肝再生不足的相关因素。结果如下：1)在肝毒素诱导的大鼠肝大量坏死中，纤维蛋白沉积在肝窦内，并伴随内皮细胞的破坏。给予灭活小棒状杆菌激活大鼠肝巨噬细胞后或部分肝切除后给予内毒素，也可观察到如此大规模的肝坏死。2)当大鼠接受部分肝切除后肝再生所必需的腐胺时，肝脏DNA合成增加，肝脏腐胺含量增加，胰岛素。胰高血糖素或表皮生长因子通过增加多胺产生的关键酶鸟氨酸脱羧酶的转录后调控，增加肝脏腐胺含量，提示肝大部切除后肝脏的多胺代谢可能为评价促肝因子的作用部位提供有用的工具。3)大鼠肝细胞质膜在表皮生长因子或肝细胞生长因子存在下，对原代培养的大鼠肝细胞的DNA合成既有刺激因子又有抑制因子。4)在肝窦纤维蛋白沉积继发的大鼠肝大量坏死中，凝血酶原时间与肝DNA合成呈负相关。用抗凝剂输注治疗后，坏死减轻。当从给予肝毒素的大鼠体内获得质膜时，其刺激肝脏增殖的潜力几乎消失。在暴发性肝衰竭中，肝脏循环障碍和肝质膜这种刺激能力的丧失可能是导致肝脏再生不足的原因之一。

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.