Study on Regulatory Mechanism of Liver Regeneration

众所周知，暴发性肝炎以严重的肝细胞坏死为基础。从这个意义上说，本申请人有一个想法，即促进肝再生可能会改善这种病理条件下的死亡率。这两年来，我们主要研究了表皮生长因子（EGF）在多大程度上可以引起这种疾病的肝再生。首先，我们对CCl_4诱发的急性肝衰竭大鼠给予EGF治疗。令人惊讶的是，在施用EGF后，可以在肝脏中诱导显著的DNA合成。与腹膜内和静脉内途径相比，在门静脉内给药的情况下，DNA合成肝细胞的数量达到最大。另一方面，我们还研究了EGF可以刺激慢性肝损伤（AOC）中携带急性肝功能衰竭的肝脏中的DNA合成，已知AOC的死亡率高于暴发性肝炎。用CCl_4慢性肝损伤的动物，给予d-氨基半乳糖，建立AOC动物模型。结果表明，外源性EGF对AOC肝细胞DNA合成无明显影响。因此，我们可以理解AOC是肝再生受损的一种情况。

It is well-known that fulminant hepatitis is based upon severe hepatic cell necrosis. In this sense, this applicant has got the idea that promotion of liver regeneration might improve the mortality in this pathologic condition.For these two years, we have mainly studied on how much Epidermal Growth Factor (EGF) can cause liver regeneration in this disease. First of all, we administered EGF into the rats carrying acute liver failure developed with CCl_4. Surprisingly, remarkable DNA synthesis could be induced in the liver after administration of EGF. Number of DNA synthesizing hepatocytes reached at maximum in case of its intra-portal administration, as compared with intra-peritoneal and intra-venous routes. On the other hand, we also investigated that EGF could stimulate DNA synthesis in the liver carrying acute liver failure on chronic liver injury (AOC) which has been known to be higher mortality than fulminant hepatitis. We developed animal model for AOC by means of administration of d-galactosamine into the animals with chronic liver injury induced with chronic treatment with CCl_4.In conclusion, exogenously administered EGF never caused the increase of DNA synthesizing hepatocytes in this condition. Therefore, we can understand AOC is a condition of impaired liver regeneration.