| 共同演者 |
Tanaka Satoshi（Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan）, Saito Yoshinobu（Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan）, Kawaguchi Tsukasa（Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan）, Shimizu Satoshi（Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan）, Shigekawa Minoru（Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan）, Kodama Takahiro（Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan）, Li Wei（Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan）, Sakamori Ryotaro（Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan）, Miyagi Takuya（Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan）, Kanto Tatsuya（Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan）, Hiramatsu Naoki（Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan）, Tatsumi Tomohide（Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan）, Takehara Tetsuo（Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan） |
| 抄録 |
Background and Aim：Continuous hepatocyte apoptosis is a hallmark for chronic viral hepatitis or non-alcoholic steatohepatitis, which is a high-risk condition for HCC. Although we have reported that continuous hepatocyte apoptosis led to HCC by using mice models generated by ablation of an anti-apoptotic protein, Bcl-xL or Mcl-1, the mechanisms of the carcinogenesis driven by apoptosis are still unveiled. Method：Hepatocyte-specific Mcl-1 KO mice, which develop spontaneous hepatocyte apoptosis and lead to HCC, were examined. Results：Apoptosis, as well as serum ALT levels, in Mcl-1 KO mice was significantly ameliorated by further genetic ablation of pro-apoptotic protein, Bak, Bax or Bid. The incidence rate of HCC in a year was significantly reduced from 69% to 0%, 17%, 13%, respectively. Associated with the amelioration of apoptosis and carcinogenesis, the increased number of 8-OHdG-positive hepatocytes in Mcl-1 KO mice was significantly decreased in double KO mice. To examine the impact of oxidative stress caused by continuous apoptosis on liver carcinogenesis, Mcl-1 KO mice were continuously fed with L-N-acetylcysteine（NAC；10g/l）, an antioxidant, in drinking water. Although NAC treatment did not affect ALT levels in Mcl-1 KO liver, it significantly decreased not only the number of 8-OHdG-positive hepatocytes but also incidence rate of HCC from 69% to 33%. Conclusion：Chronic liver injury by hepatocyte apoptosis induces oxidative stress leading to the development of HCC. |
