应用树鼩模型动态观察乙肝病毒感染过程中宿主肝内的免疫反应并对模型进行再优化

项目名称： 应用树鼩模型动态观察乙肝病毒感染过程中宿主肝内的免疫反应并对模型进行再优化

项目编号： No.81460418

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 杨春

作者单位： 广西壮族自治区肿瘤防治研究所

项目金额： 47万元

中文摘要： 本项目拟基于我们前期的研究积累和国内外相关研究领域的新进展，开展如下主要研究：对新生和成年树鼩接种不同基因型和不同剂量的HBV后，定期采集血和肝活检组织标本进行两方面的检测观察- - 1.各动物感染HBV的状态（通过检测血和肝组织的HBV感染标志、观察肝组织的病理改变）；2.肝组织内一系列编码HBV免疫相关基因以及与HBV感染相关的热点基因的mRNA表达水平。最后对动态检测观察的结果做两方面的分析- - 1.各动物的感染状态与其肝组织内的HBV免疫相关基因及某些热点基因表达水平的相关性；2. 接种不同的HBV基因型和剂量对树鼩的慢性感染率、肝组织病变进程的影响。本项目的研究结果，将可能一方面通过展现机体感染HBV过程中肝组织内免疫反应的动态变化来初步阐释HBV的感染和致病机制， 另一方面将以经过再优化的树鼩模型来推动HBV感染及其相关肝癌的研究进展。

中文关键词： 树鼩；乙型肝炎病毒；免疫反应；肝癌；动物模型

英文摘要： Based on a series of studies on tree shrews (Tupaia) infected with hepatitis B virus (HBV) in vivo carried on by our group in recent decades, and based on the new progresses in the related research fields, the present project is intended to carry out the following researches. Firstly, neonatal and adult tree shrews will be divided into several groups, which then will be inoculated respectively with different genotypes and different doses of HBV. Four weeks after inoculation, blood and liver biopsy samples will be collected regularly from all of the animals. The samples will be used to monitor the status of HBV infection, by detecting the HBV infection markers and the hepatic histopathological changes. The samples will also be used to detect the mRNA levels of a series of HBV-related immune genes and the HBV-related hot genes in liver tissue. Finally, the test results will be used to analyze the relationship between the expression levels of HBV-related immune genes or certain hot genes and the HBV-infection state of animals. The test results will also be used to analyze the influences of different HBV genotypes or doses in inoculums on the incidence of chronic HBV-infection and/or on the progress of the lesions in liver tissues of animals. The results of this project will likely to interpret preliminarily the immune mechanism underline HBV infection and pathogenesis. On the other hand, the results of this project will promote the HBV-related and HBV-associated hepatocellular carcinoma-related studies by providing a re-optimized tree shrew model.

英文关键词： Tree Shrews;Hepatitis B virus;Immune response;Hepatocellular carcinoma;Animal models