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FASN在乙型肝炎病毒轉基因小鼠中的表達及功能研究

發(fā)布時間:2018-04-13 14:15

  本文選題:乙型肝炎病毒 + FASN ; 參考:《重慶醫(yī)科大學》2014年碩士論文


【摘要】:乙型肝炎病毒是一種最常見的肝炎病毒,它能使人類遭受慢性乙型肝炎的折磨,這已經(jīng)是全球性的主要的健康問題之一。為了獲得對乙肝發(fā)病機制的進一步了解,并識別出新穎的抗病毒治療靶點,我們的研究旨在闡明HBV轉基因鼠的肝組織中差異性表達的宿主蛋白。肝臟樣本來自兩個分組:(1)HBV轉基因(Tg)小鼠,(2)相應背景的正常野生型(WT)小鼠。樣本收集后,運用iTRAQ技術和質譜分析技術進行研究。我們識別出了1950個特異蛋白,在Tg小鼠和WT小鼠的比較中,有68個蛋白差異性表達。我們選取了其中幾個差異性表達的蛋白,應用熒光實時定量PCR、蛋白印跡和免疫組織化學等方法對其差異做了進一步驗證。并且,,Tg小鼠中高差異性表達的蛋白之一——脂肪酸合成酶(FASN)與乙肝病毒復制的關系得到了進一步驗證。沉默HepG2.2.15細胞中FASN的表達能夠影響干擾素途徑及其下游抗病毒因子表達,從而抑制病毒復制。FASN在病毒復制中的潛在作用為測試現(xiàn)有的抗FASN分子作為輔助治療和/或乙肝治療提供了機會。
[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.
【學位授予單位】:重慶醫(yī)科大學
【學位級別】:碩士
【學位授予年份】:2014
【分類號】:R512.62

【參考文獻】

相關期刊論文 前2條

1 申麗娟,章宗籍,張華獻,楊微波,黃潤;肝細胞癌乙型肝炎病毒感染與人胎盤型谷胱甘肽S-轉移酶的表達[J];癌癥;2002年01期

2 ;Establishment of mice model with human viral hepatitis B[J];World Journal of Gastroenterology;2004年06期



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