【摘要】：乙型肝炎病毒(Hepatitis B virus，HBV)感染肝細(xì)胞所致肝炎、肝硬化甚至肝癌是危及全世界，尤其是我國人民健康的重要原因。盡管到目前為止，HBV的確切致病機(jī)制尚存在爭(zhēng)議，但已有研究證實(shí)，HBV感染所致肝細(xì)胞凋亡失衡不僅是乙肝患者肝細(xì)胞損傷的重要分子機(jī)制之一，，而且在乙肝患者不同的預(yù)后、轉(zhuǎn)歸中發(fā)揮著不容忽視的、甚至是決定性的作用。 眾多研究表明，TNFα、FasL等凋亡誘導(dǎo)分子在HBV感染所致肝細(xì)胞損傷中發(fā)揮重要作用。腫瘤壞死因子凋亡誘導(dǎo)配體(Tumor necrosis factor-relatedapoptosis-inducing ligand，TRAIL)是于1994年被克隆、命名的腫瘤壞死因子家族成員，其最為顯著的特點(diǎn)是：可選擇性地誘導(dǎo)腫瘤細(xì)胞或者病毒感染細(xì)胞的凋亡，而對(duì)正常組織細(xì)胞無明顯毒性。研究發(fā)現(xiàn)，許多因素(病毒／病毒編碼蛋白、射線、藥物等)可改變細(xì)胞對(duì)TRAIL誘導(dǎo)凋亡的敏感性。我室在前期研究中首次提出并報(bào)道了，HBV感染可提高肝癌細(xì)胞對(duì)TRAIL誘導(dǎo)凋亡的敏感性，可能在HBV感染所致肝細(xì)胞損傷中發(fā)揮一定的作用。但是，HBV全基因組至少包含四個(gè)開放性讀碼框架(Open reading frame，ORF)，編碼合成相應(yīng)病毒蛋白質(zhì)，那么究竟哪一個(gè)片段是導(dǎo)致HBV影響TRAIL誘導(dǎo)凋亡的關(guān)鍵性基因區(qū)段呢?這些關(guān)鍵性基因區(qū)段在TRAIL誘導(dǎo)凋亡通路中的關(guān)鍵性作用位點(diǎn)又是什么呢?因此，在前期工作的基礎(chǔ)上，本課題在國內(nèi)外率先開展了有關(guān)HBV影響TRAIL誘導(dǎo)凋亡的機(jī)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- 偽 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.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2006
【分類號(hào)】：R373

【引證文獻(xiàn)】

相關(guān)碩士學(xué)位論文 前1條

1 鄧蘭;腫瘤壞死因子凋亡相關(guān)配體（TRAIL）對(duì)乙肝病毒復(fù)制過程影響的初探[D];四川大學(xué);2007年

本文編號(hào)：2177589