發(fā)布時間：2018-04-28 15:41

  本文選題：IL-27 + gp130/CD130��； 參考：《中南大學(xué)》2014年碩士論文

【摘要】：背景：艾滋病(Acquired Immune Deficiency Syndrome, AIDS)是嚴重威脅人民健康的公共衛(wèi)生問題,隨著高效抗反轉(zhuǎn)錄病毒治療(Highly active antiretro viral therapy, HAART)的推廣,艾滋病抗病毒治療取得了一定的成效,但迄今為止仍無有效的方法徹底清除艾滋病毒(human immunodeficiency virus, HIV)。近年來,細胞因子在AIDS的發(fā)病過程及其抗病毒治療中的作用受到日益關(guān)注�？茖W(xué)家們已發(fā)現(xiàn)了多種細胞因子參與抗HIV病毒免疫應(yīng)答和免疫重建,并提出其中一些細胞因子可能成為加強抗HIV病毒效果的輔助治療手段。IL-27是HIV研究領(lǐng)域一個較新的細胞因子,已有體外實驗發(fā)現(xiàn)IL-27在HIV-1病毒感染中可能存在一定的治療價值,但IL-27相關(guān)的臨床研究較少。本文將研究HIV感染者IL-27及其受體的表達情況及其在艾滋病發(fā)病機制和HAART抗病毒治療免疫反應(yīng)中的作用。 目的：研究HIV感染者IL-27和它的受體表達情況及其與正常人的區(qū)別；HAART對IL-27和它的受體表達的影響；分析HIV感染者IL-27及其受體gp130與CD4+T細胞數(shù)、HIV-RNA病毒載量的關(guān)系,IL-27與Thl細胞因子IFN-y和Th2細胞因子IL-4的關(guān)系,進一步探索艾滋病的發(fā)病機制和免疫重建機制。 方法：從2012年12月到2013年3月來湘雅二醫(yī)院艾滋病�？崎T診就診并準備啟動HAART治療的HIV感染者/AIDS患者中選取34例納入本研究,并定期隨訪收集HAART治療開始前(0月),開始治療6月、12月的血標本。同時隨機選取健康體檢者27例作為健康對照組。使用酶聯(lián)免疫吸附試驗(enzyme-linked immunosorbent assay,ELISA)檢測血漿中IL-27、IFN-γ、IL-4的濃度,流式細胞術(shù)檢測外周血CD3+CD4+T細胞數(shù)、外周血單個核細胞(Peripheral Blood Mononuclear Cell, PBMC)中CD4+細胞表面gp130的表達情況,HIV實時熒光定量PCR測定外周血中HIV-RNA病毒載量,RT-PCR和瓊脂糖凝膠電泳檢測gp130mRNA的表達。對以上所測得數(shù)據(jù)進行統(tǒng)計學(xué)處理和相關(guān)性分析。 結(jié)果:HIV感染未治療者血漿中IL-27的平均濃度明顯低于正常人,開始HAART治療后IL-27的濃度逐漸升高,治療6月及12月后血漿中IL-27濃度明顯高于未治療前。HIV感染者PBMC中CD4+細胞表面gp130表達水平明顯低于正常人,隨著HAART抗病毒治療的進行,可逆轉(zhuǎn)這種情況,使gp130的表達逐漸增加；治療6月、12月時CD4+細胞表面gp130表達水平明顯高于未治療前。通過RT-PCR、瓊脂糖凝膠電泳半定量檢測gp130mRNA的表達水平證實了細胞表面gp130表達趨勢的變化。IL-27濃度與CD4+細胞表面gp130表達水平成正相關(guān)；IL-27和它的受體gp130均與CD4+T細胞數(shù)成正相關(guān)、與血漿HIV-RNA病毒載量成負相關(guān)。HIV感染者血漿IFN-y濃度隨著治療時間的延長越來越高,IL-4的濃度隨著治療時間的延長越來越低,其濃度水平都在向正常人群靠近。在HIV感染者中IL-27濃度的變化趨勢與IFN-y一致,與IL-4相反。 結(jié)論： 1、首次觀察到HIV病毒感染者血漿IL-27濃度低于健康人群,且隨著HAART抗病毒治療,IL-27的濃度逐漸升高；同時觀察到HIV病毒感染者IL-27的受體gp130在CD4+T細胞表面的表達水平明顯低于健康人群,隨著HAART抗病毒治療時間的延長,這種受體表達受損可以逐漸恢復(fù)。 2、發(fā)現(xiàn)HIV病毒感染者外周學(xué)IL-27的濃度及其受體gp130的表達與血漿HIV-RNA水平成負相關(guān),與CD3+CD4+T細胞數(shù)量成正相關(guān)。提示血漿中的IL-27對HIV感染者可能具有保護效應(yīng),IL-27及其受體gp130可能參與了HIV的發(fā)病機制及抗病毒免疫反應(yīng)機制。 3、IL-27的濃度變化和IFN-y與IL-4的濃度變化存在一定的關(guān)系,提示IL-27在HIV病毒感染中以炎性作用為主,且可能與Thl/Th2細胞因子失衡有關(guān)。
[Abstract]:Background: Acquired Immune Deficiency Syndrome (AIDS) is a public health problem that seriously threatens the people's health. With the promotion of high performance antiretroviral therapy (Highly active antiretro viral therapy, HAART), AIDS antiviral treatment has achieved a definite effect, but so far there are still no effective methods to eliminate it. Human immunodeficiency virus (HIV). In recent years, the role of cytokines in the pathogenesis of AIDS and its antiviral therapy has been increasingly concerned. Scientists have discovered a variety of cytokines involved in the anti HIV virus immune response and immune reconstruction, and suggest that some of its cytokines may become the strengthening of the anti HIV virus. .IL-27 is a new cytokine in the research field of HIV. It has been found that IL-27 may have some therapeutic value in HIV-1 virus infection in vitro, but there are few clinical studies on IL-27. This paper will study the expression of IL-27 and its receptor in HIV infected persons and the pathogenesis of AIDS and HAART resistance. The role of virus in the treatment of immune response.
Objective: To study the expression of IL-27 and its receptor and the difference between HIV and normal people, the effect of HAART on the expression of IL-27 and its receptor, the relationship between the number of IL-27 and its receptor gp130 and the number of CD4+T cells, the number of HIV-RNA virus, the relationship between IL-27 and Thl cytokine IFN-y and cytokines, and further explore the relationship between the IL-27 and Thl cytokine IFN-y and cytokines. The pathogenesis of AIDS and the mechanism of immune reconstruction.
Methods: from December 2012 to March 2013, 34 cases of /AIDS patients with HIV infection in the AIDS specialist clinic in Xiangya No.2 Hospital and /AIDS patients prepared to start the treatment were selected to be included in this study, and the regular follow-up collection of HAART treatment began (0 months) and began to treat the blood scale in June and December. At the same time, 27 health examiners were randomly selected as health. In the control group, enzyme-linked immunosorbent assay (ELISA) was used to detect the concentration of IL-27, IFN- gamma, and IL-4 in plasma. Flow cytometry was used to detect the number of CD3+CD4+T cells in peripheral blood, and the expression of peripheral blood mononuclear cells (Peripheral Blood Mononuclear Cell). The HIV-RNA virus load in peripheral blood was measured by CR, and the expression of gp130mRNA was detected by RT-PCR and agarose gel electrophoresis. Statistics and correlation analysis were carried out for the above data.
Results: the average concentration of IL-27 in plasma of HIV infected people was significantly lower than that of normal people, and the concentration of IL-27 increased gradually after HAART treatment. The concentration of IL-27 in plasma was significantly higher than that of.HIV infected persons in June and December. The level of gp130 expression on the surface of CD4+ cells in PBMC was significantly lower than that of normal people, with the antiviral therapy of HAART. It can reverse this situation and increase the expression of gp130 gradually. The expression level of gp130 on the surface of CD4+ cells in June and December is obviously higher than that before the treatment. The expression level of gp130mRNA by RT-PCR and agarose gel electrophoresis confirms the gp130 expression trend of the cell surface and the gp130 expression on the surface of CD4+ cells. The level of IL-27 and its receptor gp130 were positively correlated with the number of CD4+T cells. The concentration of IFN-y in the plasma of.HIV infected with HIV-RNA virus was increasing with the prolongation of the treatment time. The concentration of IL-4 was decreasing with the time of treatment, and the concentration level was close to the normal population. In HIV infection, the concentration level of the IL-4 was in the HIV infection. The change trend of IL-27 concentration was consistent with that of IFN-y, contrary to IL-4.
Conclusion:
1, the concentration of IL-27 in plasma of HIV virus infected people was lower than that of healthy people for the first time, and with HAART antiviral therapy, the concentration of IL-27 increased gradually. Meanwhile, the expression level of IL-27 receptor gp130 on the surface of CD4+T cells was obviously lower than that of the healthy population, and this receptor table was prolonged with the prolongation of the time of HAART antiviral therapy. The damage can be recovered gradually.
2, it was found that the concentration of IL-27 in peripheral study and the expression of gp130 and the expression of gp130 were negatively related to the plasma HIV-RNA level, and were positively related to the number of CD3+CD4+T cells. It suggests that IL-27 in plasma may have protective effect on HIV infected persons. IL-27 and its receptor gp130 may be involved in the pathogenesis of HIV and the mechanism of antiviral immune response.
3, the concentration changes of IL-27 and the changes of the concentration of IFN-y and IL-4 have a certain relationship, suggesting that IL-27 is mainly inflammatory in HIV virus infection, and may be related to the imbalance of Thl/Th2 cytokine.

【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R512.91

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本文編號：1815889