Studies on synergistic effects of the HBV and HCV in hepatocarcinogenesis by using transgenic mice model

转基因小鼠模型研究HBV和HCV在肝癌发生中的协同作用

• 批准号: 12670463
• 负责人: MORITA Kyoji
• 金额: $ 2.56万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670463/
• 关键词: Hepatitis C virus; transgenic mouse; ROS; hydroperoxide; alcohol; 脂質

We developed transgenic mice coexpressing hepatitis C virus (HCV) core protein and hepatitis B virus (HBV) x protein to investigate a role of HBV in hepatocarcinogenesis in patients with chronic hepatitis C and occult HBV infection.we explored the oxidant/antioxidant status in the liver of a HCV core gene transgenic mouse model of HCC in HCV infection, prior to development of HCC, by sequential quantification of hydroperoxide level, glutathione level and catalase activity and comparison of these parameters with those of age-matched non-transgenic control mice. We found an age-dependent increase in oxidative stress in the livers of transgenic mice which develop HCC in the absence of inflammation as a consequence of core protein expression. Our results indicate that the HCV core protein induces reactive oxygen species (ROS) in the liver in the absence of inflammation, which may, in part, be responsible for the development of HCC in this mouse model as well as in chronic hepatitis C patients. We also showed alcohol caused a market increase in hydroperoxide level in transgenic mice, suggesting synergism between alcohol and HCV in hepatocarcinogenesis.

我们开发了共表达丙型肝炎病毒（HCV）核心蛋白和B肝炎病毒（HBV）x蛋白的转基因小鼠，以研究HBV在慢性丙型肝炎和隐匿性HBV感染患者肝癌发生中的作用。我们通过连续定量氢过氧化物水平，谷胱甘肽水平和过氧化氢酶活性，并将这些参数与年龄匹配的非转基因对照小鼠的参数进行比较。我们发现，在没有炎症的情况下，由于核心蛋白表达，转基因小鼠肝脏中的氧化应激呈年龄依赖性增加。我们的研究结果表明，在没有炎症的情况下，HCV核心蛋白诱导肝脏中的活性氧（ROS），这可能是该小鼠模型以及慢性丙型肝炎患者中HCC发展的部分原因。我们还发现酒精引起转基因小鼠氢过氧化物水平的市场增加，表明酒精和HCV在肝癌发生中存在协同作用。

项目成果

K.Miruya, et al.: "Increase of carbon 18 mono-unsaturated fatty acids in the liver of hepatitis C, Analysis in transgenic mice and humans"Biochemical Biophysical Research Communication. (in press). (2001)

K.Miruya等人：“丙型肝炎肝脏中碳18单不饱和脂肪酸的增加，转基因小鼠和人类的分析”生化生物物理研究通讯。

Koike K, Tsutsumi T, Fujie H, Shintani Y, Moriya K: "Molecular mechanismof viral hepatocarcinogenesis"Oncology. 62 Suppl1. 20-37 (2002)

Koike K、Ttsutsumi T、Fujie H、Shintani Y、Moriya K：“病毒性肝癌发生的分子机制”肿瘤学。

Moriya K, et al.: "Oxidative stress in the absence of inflammation in a mouse model for hepatitis C virus-associated hepatocarcinogenesis"Cancer Res.. 61(11). 4365-4370 (2001)

Moriya K 等人：“丙型肝炎病毒相关肝癌发生的小鼠模型中无炎症情况下的氧化应激”Cancer Res.. 61(11)。

Shintani Y,Yotsuyanagi H,Moriga K, et al.: "The significance of hepatitis B virus DNA detected in hepatecellular carcinoma of patients with hepatitis C"Cancer. 88(11). 2478-86 (2000)

Shintani Y、Yotsuyanagi H、Moriga K 等人：“乙型肝炎病毒 DNA 在丙型肝炎患者肝细胞癌中检测的意义”癌症。

Koike K, et al.: "Molecular mechanism of viral hepatocarcinogenesis"Oncology. 62. 29-37 (2002)

Koike K 等人：“病毒性肝癌发生的分子机制”肿瘤学。