Study on Regulatory Mechanism of Liver Regeneration

众所周知，暴发性肝炎是以严重的肝细胞坏死为基础的。从这个意义上说，这个申请人已经得到了促进肝脏再生可能会改善这种病理条件下的死亡率的想法。这两年来，我们主要研究的是表皮生长因子（EGF）能在多大程度上引起这种疾病的肝脏再生。首先，我们给急性肝功能衰竭大鼠注射EGF。令人惊讶的是，EGF可以在肝脏中诱导显著的DNA合成。与腹腔和静脉给药相比，门静脉给药时肝细胞DNA合成数量最多。另一方面，我们还研究了EGF可以刺激肝脏中携带急性肝衰竭的DNA合成，慢性肝损伤（AOC）已被认为比暴发性肝炎死亡率更高。采用d-半乳糖胺给药的方法，建立慢性四氯化碳致慢性肝损伤动物模型。综上所述，外源性EGF未引起肝细胞DNA合成的增加。因此，我们可以理解AOC是肝脏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.