本文關(guān)鍵詞：慢性丙型肝炎疫苗的初步研究及肝硬化的實(shí)驗(yàn)治療　出處：《中國人民解放軍軍醫(yī)進(jìn)修學(xué)院》2005年博士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 丙型肝炎病毒NS3蛋白 多聚肌苷酸 多聚胞苷酸 細(xì)胞免疫 Montanide ISA 720 實(shí)臉性肝硬化 膠原酶 門靜脈

【摘要】：慢性病毒性肝炎和肝硬化是威脅人類健康的兩種最主要的肝臟疾病。由于乙型肝炎疫苗的發(fā)明和普及應(yīng)用,丙型肝炎在慢性病毒性肝炎的發(fā)病中發(fā)揮越來越重要的作用。因此,丙型肝炎的預(yù)防和肝硬化的治療成為肝病學(xué)者面臨的兩個最重要的任務(wù)。本文對這兩個重要問題進(jìn)行了初步的探討。 第一部分:雙鏈RNA和HCV NS3蛋白免疫小鼠可增強(qiáng)細(xì)胞免疫反應(yīng) 背景和目的:雙鏈RNA是病毒復(fù)制過程中細(xì)胞內(nèi)產(chǎn)生的一種特殊的RNA分子,它可以通過Toll蛋白樣受體3通道來誘導(dǎo)機(jī)體抗病毒免疫。HCV NS3蛋白與HCV的免疫逃逸有關(guān),也是抗HCV感染免疫的主要目標(biāo)之一。方法:小鼠用NS3重組蛋白(rNS3)和poly(I:C)混合并與Montanide ISA 720(M720)乳化后免疫小鼠。小鼠脾淋巴細(xì)胞細(xì)胞因子的產(chǎn)生用ELISPOT方法檢測,CD4~+ IFN-γ~+T輔助細(xì)胞和CD8~+ IFN-γ~+細(xì)胞毒T淋巴細(xì)胞(CTL)用流式細(xì)胞儀進(jìn)行檢測。抗-HCV NS3抗體效價及IgG2a和IgG1的含量用ELISA方法檢測。結(jié)果:細(xì)胞因子產(chǎn)生情況的分析表明,用rNS3與poly(I:C)和M720復(fù)合疫苗可以誘導(dǎo)更多的IFN-γ分泌細(xì)胞,數(shù)倍于IL-4分泌細(xì)胞,證明該疫苗可以誘導(dǎo)Th1主導(dǎo)的免疫反應(yīng)。而不加poly(I:C)的rNS3與M720復(fù)合疫苗可以誘導(dǎo)Th2主導(dǎo)的免疫反應(yīng)。rNS3與poly(I:C)和M720復(fù)合疫苗誘導(dǎo)的IFN-γ分泌細(xì)胞數(shù)量顯著多于僅用rNS3、rNS3與M720乳化或rNS3與poly(I:c)混合疫苗免疫者,而與用rNS3與CpG和M720復(fù)合疫苗誘導(dǎo)的IFN-γ分泌細(xì)胞數(shù)量相當(dāng)。另外,rNS3與poly(I:C)和M720復(fù)合疫苗誘導(dǎo)的CD8~+ IFN-γ~+ T細(xì)胞百分比與rNS3與CpG和M720復(fù)合疫苗所誘導(dǎo)的相當(dāng),這種CD8~+T細(xì)胞免疫反應(yīng)可以持續(xù)7個月以上。結(jié)論:Poly(I:C)與rNS3和M720復(fù)合疫苗可通過交叉啟動誘導(dǎo)強(qiáng)而持久的CTL反應(yīng)和Th1主導(dǎo)的免疫反應(yīng)。本研究提出了一種深具潛力的疫苗,它可以在小鼠實(shí)驗(yàn)中誘導(dǎo)增強(qiáng)的抗HCV細(xì)胞免疫,有發(fā)展為臨床應(yīng)用的HCV疫苗的潛力。 第二部分:細(xì)菌膠原酶門靜脈灌注逆轉(zhuǎn)兔實(shí)驗(yàn)性肝硬化 背景和目標(biāo):肝硬化的消退與肝內(nèi)膠原降解酶活性升高有關(guān)。本文試圖研究通過門靜脈補(bǔ)充膠原酶是否可延緩肝硬化的形成,并逆轉(zhuǎn)已形成的肝硬化。
[Abstract]:Chronic viral hepatitis and cirrhosis are the two most important liver disease threatening human health. Due to hepatitis B vaccine of the invention and application of hepatitis C, play an increasingly important role in the pathogenesis of chronic viral hepatitis. Therefore, prevention and treatment of liver cirrhosis of hepatitis C has become the two most important tasks liver disease scholars face. This paper makes a preliminary discussion on the two important issues.
Part 1: immune responses in mice immunized with double stranded RNA and HCV NS3 proteins
Background and purpose: the double stranded RNA is a special kind of RNA molecules in cells produced during viral replication, it can immune protein with Toll like receptor 3 pathway to induce antiviral immune.HCV NS3 protein and HCV on the main goal is to escape, one of the immunity against HCV infection. Methods: mice with recombinant NS3 protein (rNS3) and poly (I:C) and Montanide ISA 720 hybrid (M720) mice after emulsification. The ELISPOT method was used to detect splenocyte cytokine, CD4~+ IFN- ~+T and CD8~+ IFN- helper cell gamma gamma + cytotoxic T lymphocytes (CTL) were detected by flow cytometry. ELISA method for the determination of anti -HCV NS3 antibody titer and IgG2a and IgG1 detection. Results: analysis of cytokines produced by rNS3 and poly show that (I:C) and M720 composite vaccines can induce more IFN- gamma secreting cells, several times in the secretion of IL-4 cells, that The vaccine can induce the immune response of Th1 dominant. Without poly (I:C) rNS3 and M720 combined vaccine can induce.RNS3 and poly immune response dominated by Th2 (I:C) and IFN- gamma M720 composite vaccine induced significantly more than the number of secreting cells with only rNS3, rNS3 and M720 or rNS3 and poly emulsion (I:c) mixed vaccine, and rNS3 and CpG and M720 combined vaccine induced IFN- secreting cells in a considerable amount. In addition, rNS3 and poly (I:C) and induced by M720 composite vaccine induced CD8~+ IFN- gamma + T cell percentage and rNS3 with CpG and M720 combined vaccine, CD8~+T cell immune responses can be this over the last 7 months. Conclusion: Poly (I:C) can be induced by cross start strong and persistent CTL reaction and Th1 dominant immune response with rNS3 and M720 combined vaccine. This study presents a potential vaccine in mice, it can be experimentally induced enhancement The anti HCV cell immunization has the potential to develop the HCV vaccine for clinical application.
The second part: the reversal of rabbit experimental cirrhosis by bacterial collagenase and portal vein perfusion
Background and objective: the regression of cirrhosis is related to the increased activity of collagen degrading enzymes in the liver. This paper attempts to study whether collagenase supplementation through portal vein can retard the formation of cirrhosis and reverse the formation of cirrhosis.

【學(xué)位授予單位】：中國人民解放軍軍醫(yī)進(jìn)修學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2005
【分類號】：R392;R575.2

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 金博,李玉彬,王援朝,王立秋;氯胺T法測定羥脯氨酸含量的方法改進(jìn)[J];陜西醫(yī)學(xué)檢驗(yàn);1994年03期

，

本文編號：1377828