本文選題：丙型病毒性肝炎 + NS3��； 參考：《中國人民解放軍軍事醫(yī)學(xué)科學(xué)院》2006年博士論文

【摘要】：丙型病毒性肝炎是一種嚴(yán)重危害人類健康的常見病和多發(fā)病。全球大約有1.7億的人口感染丙型肝炎病毒(Hepatitis C Virus，HCV)。我國HCV感染者已達(dá)6000萬。HCV急性感染后50-80％轉(zhuǎn)變?yōu)槁愿腥荆渲械?0-20％發(fā)展成肝硬化，并與肝細(xì)胞癌的發(fā)生密切相關(guān)。迄今α-干擾素和病毒唑聯(lián)合治療是唯一的治療方法，但這種治療方法只對不到50％的患者顯效，且具有費(fèi)用高、易復(fù)發(fā)和副作用多等缺陷；尤其是我國流行的HCV 1b型，對α干擾素的治療應(yīng)答最低，因此，加強(qiáng)對HCV防治的研究至關(guān)重要。 HCV為單股正鏈RNA病毒，屬黃病毒科，全長約9600個核苷酸，ORF區(qū)編碼3010個氨基酸的多聚蛋白前體，經(jīng)過宿主和病毒本身基因編碼的蛋白酶裂解為十個功能性片段，包括4個結(jié)構(gòu)蛋白(核心蛋白C、包膜蛋白E1、E2以及P7)及6個非結(jié)構(gòu)蛋白(NS2、NS3、NS4A、NS4B、NS5A和NS5B)。HCV RNA 5’端沒有帽子結(jié)構(gòu)，由5’非編碼區(qū)(NCR)內(nèi)的內(nèi)部核糖體進(jìn)入位點(diǎn)(IRES)介導(dǎo)啟動并控制著整個HCV基因組的翻譯過程，而HCV NS3蛋白具有絲氨酸蛋白酶和解旋酶活性，，參與病毒蛋白翻譯后加工，為病毒復(fù)制所必須。因此IRES及HCV NS3／4A絲氨酸蛋白酶是目前抗病毒治療研究的主要靶位。 多年來針對HCV NS3／4A及HCV IRES抑制劑的研究取得可喜的進(jìn)展，但由于缺乏理想的小動物模型，這些藥物在體內(nèi)抗HCV的作用效果，以及對其毒性、安全性等難以作出評估，極大地延緩了這些藥物進(jìn)入臨床，因而建立適用于HCV IRES和NS3蛋白抑制劑篩選及評價小鼠模型迫在眉睫。
[Abstract]:Hepatitis C is a common and frequent disease that seriously endangers human health. About 170 million people worldwide are infected with hepatitis C virus. In China, 50-80% of patients infected with HCV have been transformed into chronic infection after acute infection, of which 10-20% have developed into cirrhosis, which is closely related to the occurrence of hepatocellular carcinoma (HCC). Up to now, interferon 偽 combined with ribavirin is the only treatment method, but it is effective only for less than 50% of the patients, and has many defects, such as high cost, easy to relapse and many side effects, especially the prevalent HCV 1b type in our country. Interferon alpha has the lowest therapeutic response, so it is very important to strengthen the research on the prevention and treatment of HCV. HCV is a single-stranded positive strand RNA virus, belonging to the family flaviridae. It encodes a polypeptide precursor of 3010 amino acids with a total length of 9600 nucleotides. The protease encoded by the host gene and the virus itself cleavage into ten functional fragments. There are four structural proteins (core protein C, envelope protein E1, E2, and P7) and six nonstructural proteins, NS2NS2NS3, NS4AN4NS4BN5A and NS5B).HCV RNA 5', which have no cap structure. IRES, an internal ribosomal entry site in the 5'noncoding region, initiates and controls the translation process of the entire HCV genome. The HCV NS3 protein has the activities of serine protease and helicase, and participates in the post-translation processing of virus proteins. Necessary for virus replication. Therefore, IRES and HCV NS3/4A serine protease are the main targets of antiviral therapy. Over the years, great progress has been made in the study of HCV NS3/4A and HCV IRES inhibitors. However, due to the lack of ideal small animal models, it is difficult to evaluate the effect of these drugs on HCV in vivo, as well as their toxicity and safety. Therefore, it is urgent to establish a mouse model suitable for screening and evaluating HCV IRES and NS3 protein inhibitors.
【學(xué)位授予單位】：中國人民解放軍軍事醫(yī)學(xué)科學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2006
【分類號】：R-332

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