FASN在乙型肝炎病毒转基因小鼠中的表达及功能研究

发布时间：2018-04-13 14:15

本文选题：乙型肝炎病毒 + FASN　；参考：《重庆医科大学》2014年硕士论文

【摘要】：乙型肝炎病毒是一种最常见的肝炎病毒，它能使人类遭受慢性乙型肝炎的折磨，这已经是全球性的主要的健康问题之一。为了获得对乙肝发病机制的进一步了解，并识别出新颖的抗病毒治疗靶点，我们的研究旨在阐明HBV转基因鼠的肝组织中差异性表达的宿主蛋白。肝脏样本来自两个分组：（1）HBV转基因（Tg）小鼠，（2）相应背景的正常野生型（WT）小鼠。样本收集后，运用iTRAQ技术和质谱分析技术进行研究。我们识别出了1950个特异蛋白，在Tg小鼠和WT小鼠的比较中，有68个蛋白差异性表达。我们选取了其中几个差异性表达的蛋白，应用荧光实时定量PCR、蛋白印迹和免疫组织化学等方法对其差异做了进一步验证。并且，，Tg小鼠中高差异性表达的蛋白之一——脂肪酸合成酶（FASN）与乙肝病毒复制的关系得到了进一步验证。沉默HepG2.2.15细胞中FASN的表达能够影响干扰素途径及其下游抗病毒因子表达，从而抑制病毒复制。FASN在病毒复制中的潜在作用为测试现有的抗FASN分子作为辅助治疗和/或乙肝治疗提供了机会。
[Abstract]:Hepatitis B virus (HBV) is one of the most common hepatitis viruses. It can make people suffer from chronic hepatitis B, which is one of the major global health problems.In order to further understand the pathogenesis of hepatitis B and identify novel antiviral targets, our study aims to elucidate the differentially expressed host proteins in the liver tissues of HBV transgenic mice.The liver samples were collected from two groups of normal wild type WTM mice with a corresponding background.After sample collection, iTRAQ and mass spectrometry were used to study.We identified 1950 specific proteins, 68 of which were differentially expressed in TG mice and WT mice.Several differentially expressed proteins were selected and further verified by real-time fluorescence quantitative PCR, Western blot and immunohistochemistry.The relationship between fatty acid synthase (FASNs), one of the highly differentially expressed proteins in TG mice, and hepatitis B virus replication was further verified.Silencing the expression of FASN in HepG2.2.15 cells can affect the expression of interferon pathway and its downstream antiviral factors.Thus inhibiting the potential role of virus replication. FASN in viral replication provides an opportunity to test existing anti FASN molecules as adjuvant therapy and / or hepatitis B therapy.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R512.62

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