【摘要】：背景與目的:在聯(lián)合抗反轉(zhuǎn)錄病毒治療(Combined antiretroviral therapy,cART)治療下,絕大多數(shù)HIV感染者可以達(dá)到持續(xù)的病毒抑制,但是15-30%的HIV感染者在病毒長(zhǎng)期完全抑制的情況下,CD4+T淋巴細(xì)胞數(shù)仍不能得到滿意的恢復(fù),這種現(xiàn)象稱為免疫重建不全(Incomplete immune reconstitution),而免疫重建不全的感染者稱為免疫無應(yīng)答者(Immunenon-responders,INRs)和免疫部分應(yīng)答者。免疫重建不全發(fā)生的重要機(jī)制之一是多種原因所致的免疫激活,而免疫激活又對(duì)HIV相關(guān)非AIDS并發(fā)癥的發(fā)生以及HIV儲(chǔ)存庫(kù)的維持起到促進(jìn)作用。本研究旨在探究雷公藤,一種臨床上在多種自身免疫性疾病中廣泛應(yīng)用的免疫抑制劑,是否可以抑制慢性期艾滋病免疫重建不全患者的免疫激活,影響其病毒儲(chǔ)存庫(kù),并通過與未經(jīng)雷公藤治療的免疫重建不良者進(jìn)行對(duì)照,探究雷公藤能否對(duì)免疫重建不全者的CD4+T細(xì)胞計(jì)數(shù)和增長(zhǎng)速率起到持續(xù)的改善作用。方法:從北京協(xié)和醫(yī)院艾滋病診療中心選出18例符合免疫重建不全定義的HIV感染者,在cART基礎(chǔ)上加用治療量的雷公藤多甙片(20mgtid),持續(xù)1年,每3個(gè)月規(guī)律隨訪,1年后停止雷公藤治療后每6個(gè)月隨訪,收集臨床資料并留取外周血標(biāo)本,測(cè)定外周血T淋巴細(xì)胞亞群,留取全血、血漿凍存,后續(xù)分別用來測(cè)量總HIV-DNA和血漿炎癥因子水平�；仡櫺缘膹谋本﹨f(xié)和醫(yī)院艾滋病診療中心的就診患者中篩選符合免疫重建不全定義,且年齡與實(shí)驗(yàn)組匹配的患者作為對(duì)照組,對(duì)比實(shí)驗(yàn)組與對(duì)照組在雷公藤治療相應(yīng)cART治療時(shí)間段內(nèi)CD4+T細(xì)胞增長(zhǎng)情況。結(jié)果:1、雷公藤對(duì)免疫重建不全者外周血CD4+T細(xì)胞計(jì)數(shù)的影響對(duì)于實(shí)驗(yàn)組患者,雷公藤聯(lián)合cART治療12月可使CD4+T細(xì)胞計(jì)數(shù)顯著增長(zhǎng)(由188±61/μl增至272±79/μl,p0.0001)。CD4+ T細(xì)胞計(jì)數(shù)增長(zhǎng)以記憶CD4+ T細(xì)胞為主。實(shí)驗(yàn)組平均在cART治療2.5年加用雷公藤治療,雷公藤治療期間CD4+T細(xì)胞計(jì)數(shù)增長(zhǎng)速率較雷公藤治療前增長(zhǎng)速率增高(34.0 cells/mm3/年增至82.0 cells/mm3/年,p=0.077);實(shí)驗(yàn)組雷公藤停藥后CD4+T細(xì)胞增長(zhǎng)速率顯著低于雷公藤治療期間速率(82.0cells/mm3/年to23.5cells/mm3/年);非雷公藤組cART治療0.5-3.5年間CD4+T細(xì)胞增長(zhǎng)速率為27 cells/mm3/年,顯著低于實(shí)驗(yàn)組雷公藤治療期間CD4+T細(xì)胞增長(zhǎng)速率(p=0.022)。2、雷公藤對(duì)實(shí)驗(yàn)組患者血漿炎癥因子的影響對(duì)雷公藤治療組患者開始加用雷公藤多甙治療的1年前、雷公藤治療基線(0年)、加用雷公藤0.5年、加用雷公藤1年,共4個(gè)隨訪點(diǎn)留取的血漿用液相芯片法對(duì) 13 種炎癥因子進(jìn)行測(cè)量。IP-10、MIP-1β、MCP-1、IFN-α2、IL-15、IL-12p40在加用雷公藤多甙治療后較治療前顯著下降(至少在雷公藤治療半年或治療1年較雷公藤治療0年有顯著下降,p0.05)。IP-10與兩種干擾素的相關(guān)性分析提示,IP-10濃度與IFNγ具有顯著正相關(guān)性。3、雷公藤治療組患者HIV儲(chǔ)存庫(kù)的變化情況雷公藤治療前、治療中、治療后免疫重建不全患者HIV儲(chǔ)存庫(kù)的變化率無明顯變化。結(jié)論:1、雷公藤多甙可顯著提高HIV感染免疫重建不全患者外周血CD4+ T淋巴細(xì)胞計(jì)數(shù)和CD4+T細(xì)胞增長(zhǎng)速度,以記憶CD4+T細(xì)胞的增長(zhǎng)為主,但CD4+T細(xì)胞計(jì)數(shù)增長(zhǎng)速度的提高在停藥后不能持續(xù)。2、免疫重建不全的患者血漿 IP-10、MIP-1β、MCP-1、IFN-α2、IL-15、IL-12p40水平在加用雷公藤多甙治療后較治療前顯著下降,以IP-10下降最為顯著;IP-10濃度與IFNγ具有顯著正相關(guān)性。3、雷公藤多甙聯(lián)合cART治療對(duì)于免疫重建不全患者的HIV儲(chǔ)存庫(kù)未發(fā)現(xiàn)有明顯影響。
[Abstract]:Background and purpose: under the treatment of Combined antiretroviral therapy (cART), the overwhelming majority of HIV infected persons can achieve continuous viral inhibition, but the number of CD4+T lymphocytes in 15-30% HIV infected persons is still not satisfactory in the case of long-term complete inhibition of the virus. This phenomenon is called immunization. Incomplete immune reconstitution, and immune reconstructive infections are known as immune non responders (Immunenon-responders, INRs) and immune responses. One of the important mechanisms of immune reconstruction is a variety of causes of immune activation, and immune activation is also responsible for the occurrence of non AIDS complications related to HIV and the occurrence of HIV related complications. The purpose of this study is to explore the effect of the maintenance of the HIV repository. The purpose of this study is to explore the widely used immunosuppressants in many autoimmune diseases, which can inhibit the immune activation of patients with chronic AIDS immune reconstitution, affect their virus storage and through immune reconstruction with untreated Tripterygium wilfordii. To investigate whether Tripterygium wilfordii can continue to improve the CD4+T cell count and growth rate of immune reconstructive patients. Methods: 18 cases of HIV infected by immunoreconstruction were selected from the AIDS diagnosis and treatment center of Peking Union Medical College Hospital, and the dose of Tripterygium wilfordii (20mgtid) was added on the basis of cART. After 1 years, follow up every 3 months and 1 years after 1 years to stop the follow-up of Tripterygium wilfordii, collect the clinical data and leave the peripheral blood samples, determine the peripheral blood T lymphocyte subgroup, leave the whole blood, the plasma cryopreservation, then measure the total HIV-DNA and plasma inflammatory factors respectively. In the patients with heart disease, the patients who were matched with the experimental group were selected as the control group, and the CD4+T cell growth in the corresponding cART treatment period was compared between the experimental group and the control group. Results: 1, the effect of Tripterygium wilfordii on the peripheral blood CD4+T cell count in the patients with immune reconstitution insufficiency was in the experimental group. Patients, Tripterygium wilfordii combined with cART treatment in December can increase the number of CD4+T cells significantly (from 188 + 61/ Mu l to 272 + 79/ L, P0.0001).CD4+ T cell count increase to memory CD4+ T cells. The experimental group was treated with Tripterygium Wilfordii in 2.5 years of cART treatment, and the growth rate of cell count increased before Tripterygium wilfordii treatment. The rate increased (34 cells/mm3/ years to 82 cells/mm3/ years, p=0.077), and the rate of CD4+T cell growth after Tripterygium wilfordii was significantly lower than that of Tripterygium wilfordii (82.0cells/mm3/ year to23.5cells/mm3/). The CD4+T fine cell growth rate of non Tripterygium group cART treatment was 27 cells/mm3/ years, which was significantly lower than that of the experimental group. CD4+T cell growth rate (p=0.022).2 during the treatment of rattan, the effect of Tripterygium wilfordii on the plasma inflammatory factors of the patients in the experimental group was 1 years before the Tripterygium wilfordii treatment group was treated with Tripterygium wilfordii (0 years), 0.5 years with Tripterygium wilfordii, plus 1 years of Tripterygium wilfordii, and a total of 4 follow up points for plasma liquid chromatography 13 kinds of inflammatory factors were measured.IP-10, MIP-1 beta, MCP-1, IFN- alpha 2, IL-15, IL-12p40 were significantly lower than before treatment with Tripterygium wilfordii treatment (at least in the treatment of Tripterygium wilfordii for six months or 1 years compared with Tripterygium wilfordii treatment 0 years, P0.05).IP-10 and two kinds of interferon analysis suggested that IP-10 concentration and IFN gamma have significant With positive correlation.3 and the changes of HIV storage in Tripterygium wilfordii treatment group, before Tripterygium wilfordii treatment, there was no significant change in the change rate of HIV storage in patients with immune reconstruction after treatment. Conclusion: 1, Tripterygium wilfordii can significantly increase the number of CD4+ T lymphocyte counts and CD4+T cell growth rate in peripheral blood of patients with HIV infection. The growth of CD4+T cells was mainly in memory, but the increase in the growth rate of CD4+T cell counts was not sustained after the withdrawal of.2. The plasma IP-10, MIP-1 beta, MCP-1, IFN- alpha 2, IL-15, and IL-12p40 were significantly decreased after the treatment with Tripterygium wilfordii, and the most significant decreased with IP-10. IP-10 concentration and IFN gamma were the most significant. There was a significant positive correlation between.3. Tripterygium glycosides combined with cART treatment had no significant effect on HIV storage in patients with incomplete immune reconstitution.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：R512.91

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