HBV感染影响TRAIL诱导凋亡关键基因片段的筛选及其分子机制的研究
发布时间：2018-08-11 16:33
【摘要】：乙型肝炎病毒(Hepatitis B virus，HBV)感染肝细胞所致肝炎、肝硬化甚至肝癌是危及全世界，尤其是我国人民健康的重要原因。尽管到目前为止，HBV的确切致病机制尚存在争议，但已有研究证实，HBV感染所致肝细胞凋亡失衡不仅是乙肝患者肝细胞损伤的重要分子机制之一，，而且在乙肝患者不同的预后、转归中发挥着不容忽视的、甚至是决定性的作用。 众多研究表明，TNFα、FasL等凋亡诱导分子在HBV感染所致肝细胞损伤中发挥重要作用。肿瘤坏死因子凋亡诱导配体(Tumor necrosis factor-relatedapoptosis-inducing ligand，TRAIL)是于1994年被克隆、命名的肿瘤坏死因子家族成员，其最为显著的特点是：可选择性地诱导肿瘤细胞或者病毒感染细胞的凋亡，而对正常组织细胞无明显毒性。研究发现，许多因素(病毒／病毒编码蛋白、射线、药物等)可改变细胞对TRAIL诱导凋亡的敏感性。我室在前期研究中首次提出并报道了，HBV感染可提高肝癌细胞对TRAIL诱导凋亡的敏感性，可能在HBV感染所致肝细胞损伤中发挥一定的作用。但是，HBV全基因组至少包含四个开放性读码框架(Open reading frame，ORF)，编码合成相应病毒蛋白质，那么究竟哪一个片段是导致HBV影响TRAIL诱导凋亡的关键性基因区段呢?这些关键性基因区段在TRAIL诱导凋亡通路中的关键性作用位点又是什么呢?因此，在前期工作的基础上，本课题在国内外率先开展了有关HBV影响TRAIL诱导凋亡的机制研究，并取得了一定的研究成果。
[Abstract]:Hepatitis B virus (Hepatitis B virus) infection of liver cells, liver cirrhosis and even liver cancer is an important cause of endangering the health of people all over the world, especially in our country. Although the exact pathogenesis of HBV is still controversial, it has been confirmed that the imbalance of hepatocyte apoptosis induced by HBV infection is not only one of the important molecular mechanisms of hepatocyte injury in patients with hepatitis B, but also has different prognosis in patients with hepatitis B. The result plays an important and even decisive role. Many studies have shown that apoptosis-inducing molecules such as TNF- 伪 and FasL play an important role in hepatocyte injury induced by HBV infection. Tumor necrosis factor apoptosis-inducing ligand (Tumor necrosis factor-relatedapoptosis-inducing ligand trail) is a member of tumor necrosis factor family cloned in 1994. Its most significant feature is that it can selectively induce apoptosis of tumor cells or virus infected cells. However, there was no obvious toxicity to normal tissue and cells. It has been found that many factors (virus / virus encoded proteins, rays, drugs, etc.) can change the sensitivity of cells to TRAIL induced apoptosis. In our previous study, we proposed and reported for the first time that HBV infection can enhance the sensitivity of hepatoma cells to TRAIL induced apoptosis, and may play a role in the damage of hepatocytes induced by HBV infection. However, the whole genome of (Open reading contains at least four open reading frames (Open reading frame ORF), which encodes and synthesizes the corresponding viral proteins. So which fragment is the key gene that causes HBV to induce apoptosis in TRAIL? What are the key roles of these key gene segments in the TRAIL induced apoptosis pathway? Therefore, on the basis of the previous work, the research on the mechanism of HBV affecting apoptosis induced by TRAIL has been carried out first at home and abroad, and some research results have been obtained.
【学位授予单位】：山东大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R373
本文编号：2177589
[Abstract]:Hepatitis B virus (Hepatitis B virus) infection of liver cells, liver cirrhosis and even liver cancer is an important cause of endangering the health of people all over the world, especially in our country. Although the exact pathogenesis of HBV is still controversial, it has been confirmed that the imbalance of hepatocyte apoptosis induced by HBV infection is not only one of the important molecular mechanisms of hepatocyte injury in patients with hepatitis B, but also has different prognosis in patients with hepatitis B. The result plays an important and even decisive role. Many studies have shown that apoptosis-inducing molecules such as TNF- 伪 and FasL play an important role in hepatocyte injury induced by HBV infection. Tumor necrosis factor apoptosis-inducing ligand (Tumor necrosis factor-relatedapoptosis-inducing ligand trail) is a member of tumor necrosis factor family cloned in 1994. Its most significant feature is that it can selectively induce apoptosis of tumor cells or virus infected cells. However, there was no obvious toxicity to normal tissue and cells. It has been found that many factors (virus / virus encoded proteins, rays, drugs, etc.) can change the sensitivity of cells to TRAIL induced apoptosis. In our previous study, we proposed and reported for the first time that HBV infection can enhance the sensitivity of hepatoma cells to TRAIL induced apoptosis, and may play a role in the damage of hepatocytes induced by HBV infection. However, the whole genome of (Open reading contains at least four open reading frames (Open reading frame ORF), which encodes and synthesizes the corresponding viral proteins. So which fragment is the key gene that causes HBV to induce apoptosis in TRAIL? What are the key roles of these key gene segments in the TRAIL induced apoptosis pathway? Therefore, on the basis of the previous work, the research on the mechanism of HBV affecting apoptosis induced by TRAIL has been carried out first at home and abroad, and some research results have been obtained.
【学位授予单位】：山东大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R373
【引证文献】
相关硕士学位论文 前1条
1 邓兰;肿瘤坏死因子凋亡相关配体（TRAIL）对乙肝病毒复制过程影响的初探[D];四川大学;2007年
本文编号：2177589
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