本文關鍵詞：慢性丙型肝炎疫苗的初步研究及肝硬化的實驗治療　出處：《中國人民解放軍軍醫(yī)進修學院》2005年博士論文　論文類型：學位論文

  更多相關文章： 丙型肝炎病毒NS3蛋白 多聚肌苷酸 多聚胞苷酸 細胞免疫 Montanide ISA 720 實臉性肝硬化 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,丙型肝炎的預防和肝硬化的治療成為肝病學者面臨的兩個最重要的任務。本文對這兩個重要問題進行了初步的探討。 第一部分:雙鏈RNA和HCV NS3蛋白免疫小鼠可增強細胞免疫反應 背景和目的:雙鏈RNA是病毒復制過程中細胞內產生的一種特殊的RNA分子,它可以通過Toll蛋白樣受體3通道來誘導機體抗病毒免疫。HCV NS3蛋白與HCV的免疫逃逸有關,也是抗HCV感染免疫的主要目標之一。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。小鼠脾淋巴細胞細胞因子的產生用ELISPOT方法檢測,CD4~+ IFN-γ~+T輔助細胞和CD8~+ IFN-γ~+細胞毒T淋巴細胞(CTL)用流式細胞儀進行檢測�？�-HCV NS3抗體效價及IgG2a和IgG1的含量用ELISA方法檢測。結果:細胞因子產生情況的分析表明,用rNS3與poly(I:C)和M720復合疫苗可以誘導更多的IFN-γ分泌細胞,數(shù)倍于IL-4分泌細胞,證明該疫苗可以誘導Th1主導的免疫反應。而不加poly(I:C)的rNS3與M720復合疫苗可以誘導Th2主導的免疫反應。rNS3與poly(I:C)和M720復合疫苗誘導的IFN-γ分泌細胞數(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復合疫苗誘導的IFN-γ分泌細胞數(shù)量相當。另外,rNS3與poly(I:C)和M720復合疫苗誘導的CD8~+ IFN-γ~+ T細胞百分比與rNS3與CpG和M720復合疫苗所誘導的相當,這種CD8~+T細胞免疫反應可以持續(xù)7個月以上。結論:Poly(I:C)與rNS3和M720復合疫苗可通過交叉啟動誘導強而持久的CTL反應和Th1主導的免疫反應。本研究提出了一種深具潛力的疫苗,它可以在小鼠實驗中誘導增強的抗HCV細胞免疫,有發(fā)展為臨床應用的HCV疫苗的潛力。 第二部分:細菌膠原酶門靜脈灌注逆轉兔實驗性肝硬化 背景和目標:肝硬化的消退與肝內膠原降解酶活性升高有關。本文試圖研究通過門靜脈補充膠原酶是否可延緩肝硬化的形成,并逆轉已形成的肝硬化。
[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.

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

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相關期刊論文 前1條

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本文編號：1377828