Molecular investigation on the fulminant hepatitis-resistant model animals

暴发性肝炎耐药模型动物的分子研究

基本信息

批准号：
10470253
负责人：
MIURA Naoyuki
金额：
$ 8.38万
依托单位：
HAMAMATSU UNIVERSITY SCHOOL OF MEDICINE (1999-2000)Akita University (1998)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10470253/
关键词：
Rb protein Transgenic mice Apoptosis Fulminant hepatitis Fas antigen TNFα Hepatocellular carcinoma Nodule トランスジェニックマウス HNF1 化学発癌 GOT 肝細胞変性出血トランスジーン

项目摘要

Two lines of the transgenic mice in which the human Rb cDNA was controlled under the) kbp of rat hepatocyte nuclear factor-1 (HNF-1) promoter/enhancer were generated. Transgenic mice, line A (TGA) had about 11 copies of the transgenes per haploid and line B (TGB) had about 4 copies of the transgenes. By Western blot analysis, we observed that a large amount of Rb protein was expressed in the liver of TGA mice and a small amount of Rb protein was expressed in that of TGB mice. In control mice, injection of anti-Fas antibody and TNFα induced increase of GOT and GPT in serum, hemorrhages and hepatocyte apoptosis in the histology. However, in TGA mice, the increase in GOT and GPT was marginal and no hemorrhages and apoptosis were detected In TGB mice, the increase in GOT and GPT was moderate and apoptosis of the substantial number of hepatocytes was observed, but no hemorrhages. In order to investigate the molecular mechanism of anti-apoptotic condition, we did the western blot analysis of … More apoptosis-related proteins. Fas, Bcl-2, Bcl-X, Bid, Bad, ICE, CPP32, E2F1, E2F2, E2F3, E2F4, E2F5 and p53 proteins had no differences between control mice and Rb transgenic mice. However, the Bax protein was decreased in Rb transgenic mice compared to control mice. This suggests that the Bax protein is on e of the contributing proteins for the anti-apoptotic condition.Next we investigated whether the Rb transgenic mice showed resistance to chemical carcinogenesis. We inject diethylnitrosamine into the peritoneal cavity at the age of 6 weeks and treated phenobarbital in drinking water for 35 weeks. After the experiment, the mice were sacrificed to make histological sections for counting the numbers of hepatocellular carcinoma and hepatic nodule. In control mice, a large number of nodules and several hepatocellular carcinoma were developed. In contrast, the number of nodules was greatly reduced and no hepatocellular carcinomas were detected in Rb transgenic mice. These results indicate that the Rb protein act as an anti apoptotic agent and an anti-tumorigenic agent in the liver in vivo. Less

产生的WHMPATOCYTE核因子1（HNF-1）启动子/增强子中的两条转基因小鼠。在TGA小鼠的肝脏中，通过蛋白质印迹分析在TGB小鼠的肝脏中被散布在TGB小鼠的肝脏中。然而，在TGA小鼠中，GPT的增加和GPT是边缘的，没有出血，没有出血，以调查抗抑制节的分子机制，我们进行了抗焦点的分子机制。与凋亡相关的蛋白质。 - 凋亡条件。我们研究了RB转基因小鼠是否显示出表现出的表现为化学癌的发生。在对照小鼠中，在RB癌中发现了大量结节性肝细胞癌的肝细胞癌和肝结节。体内