發(fā)布時(shí)間：2018-05-24 08:19

  本文選題：3型天然淋巴細(xì)胞 + 人類免疫缺陷病毒1型　； 參考：《中國(guó)人民解放軍醫(yī)學(xué)院》2016年博士論文

【摘要】：第一部分HIV-1感染者ILC3s的變化及臨床意義HIV-1感染后引起的異常免疫激活可導(dǎo)致抗病毒治療后免疫重建失敗、非艾滋相關(guān)事件發(fā)生率增加等臨床難題。腸道黏膜屏障受損導(dǎo)致腸道微生物易位是可能的原因之一。鑒于3型天然淋巴細(xì)胞(group 3 innate lymphoid cells, ILC3s)在腸黏膜屏障功能的維持中發(fā)揮重要作用,為探討ILC3s在HIV-1感染者中的變化及意義,本研究利用流式細(xì)胞術(shù)檢測(cè)了HIV-1感染者外周血的ILC3s頻率,發(fā)現(xiàn)HIV-1感染者外周血ILC3s頻率降低.并與標(biāo)志病情進(jìn)展程度的病毒載量、CD4+T細(xì)胞數(shù)量和CD4/CD8比值相關(guān);應(yīng)用免疫組織化學(xué)方法檢測(cè)HIV-1感染者腸黏膜組織中的ILC3s也較非HIV-1感染者減少;進(jìn)一步研究ILC3s減少的機(jī)制發(fā)現(xiàn),HIV-1感染者ILC3s表達(dá)CD95和活化caspase-3的水平升高,提示CD95/FasL途徑介導(dǎo)的凋亡是ILC3s減少的原因之一;為研究ILC3s減少的臨床意義,我們檢測(cè)了反映微生物易位的脂多糖(LPS)及可溶性CD14 (sCD14)水平,發(fā)現(xiàn)HIV-1感染者外周血ILC3s頻率與LPS和sCD14呈負(fù)相關(guān),提示ILC3s的降低導(dǎo)致了腸道微生物易位。在第一部分中,我們認(rèn)為HIV-1感染通過CD95/FasL途徑介導(dǎo)細(xì)胞凋亡導(dǎo)致外周血和腸黏膜ILC3s的降低,從而導(dǎo)致腸黏膜屏障功能的破壞,引起微生物易位,以及后續(xù)的免疫激活等問題。第二部分埃博拉病毒病的臨床診治2013年12月起,西非地區(qū)爆發(fā)了歷史上最大的一次埃博拉病毒病大流行,塞拉利昂是疫情最為嚴(yán)重的國(guó)家,為幫助該國(guó)處置疫情,解放軍第302醫(yī)院先后抽組5批次醫(yī)療隊(duì)赴塞拉利昂首都弗里敦執(zhí)行援非抗疫任務(wù)。本研究回顧性總結(jié)了確診患者的臨床資料,發(fā)現(xiàn)患者年齡分布以18-40歲為主,病死率隨年齡、病毒載量升高而遞增,生存時(shí)間隨之遞減,癥狀以發(fā)熱、腹痛、腹瀉等為主,腹瀉、乏力和吞咽困難等在死亡組的發(fā)生率顯著高于存活組。多因素分析發(fā)現(xiàn)年齡、病毒載量和有無腹瀉癥狀與生存時(shí)間相關(guān),年齡大、病毒載量高和有腹瀉癥狀的屬于高�；颊�,生存時(shí)間較短;在醫(yī)療資源緊張和缺乏特效抗病毒藥物的條件下,將靜脈補(bǔ)液等支持治療手段優(yōu)先用于這部分患者可能降低病死率。
[Abstract]:The changes of ILC3s in patients with HIV-1 infection and its clinical significance the abnormal immune activation caused by HIV-1 infection may lead to the failure of immune reconstruction after antiviral therapy and the increasing incidence of non-AIDS-related events and other clinical problems. One of the possible reasons for intestinal microbial translocation is intestinal mucosal barrier damage. In view of the important role of type 3 natural lymphocyte group 3 innate lymphoid cells, ILC3s in the maintenance of intestinal mucosal barrier function, in order to investigate the changes and significance of ILC3s in HIV-1 infected patients, the frequency of ILC3s in peripheral blood of HIV-1 infected patients was detected by flow cytometry. The frequency of ILC3s in peripheral blood of HIV-1 infected patients was decreased. The number of CD4 T cells and the ratio of CD4/CD8 were correlated with the viral load and the ratio of CD4/CD8, and the number of ILC3s in intestinal mucosa of HIV-1 infected patients was lower than that of non-HIV-1 infected patients. Further study on the mechanism of ILC3s reduction found that the level of ILC3s expression and activated caspase-3 increased in HIV-1 infected patients, suggesting that apoptosis mediated by CD95/FasL pathway is one of the causes of ILC3s decrease, and in order to study the clinical significance of ILC3s reduction, We detected the levels of lipopolysaccharide (LPS) and soluble CD14 (CD14) in peripheral blood of HIV-1 infected patients, and found that the frequency of ILC3s in peripheral blood was negatively correlated with LPS and sCD14, suggesting that the decrease of ILC3s resulted in intestinal microbial translocation. In the first part, we believe that HIV-1 infection mediated apoptosis through CD95/FasL pathway leads to the decrease of ILC3s in peripheral blood and intestinal mucosa, which leads to the destruction of intestinal mucosal barrier function, microbial translocation, and subsequent immune activation. The second part of the clinical diagnosis and treatment of Ebola virus disease since December 2013, the West African region has the largest Ebola epidemic in history, Sierra Leone is the most severely affected country, to help the country to deal with the epidemic. PLA 302 Hospital drew 5 batches of medical teams to Freetown, Sierra Leone, to carry out anti-African missions. The clinical data of the patients were summarized retrospectively. It was found that the age distribution of the patients was mainly 18-40 years old, the mortality increased with age, the viral load increased, the survival time decreased, the symptoms were fever, abdominal pain, diarrhea, etc. The incidence of fatigue and dysphagia was significantly higher in the death group than in the surviving group. Multivariate analysis showed that age, viral load and diarrhea symptoms were associated with survival time. The patients with high viral load and diarrhea symptoms were at high risk and had shorter survival time. Under the condition of shortage of medical resources and lack of special antiviral drugs, it is possible to reduce the mortality rate by using the support therapy such as intravenous fluid resuscitation in this group of patients.
【學(xué)位授予單位】：中國(guó)人民解放軍醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R512.8;R512.91

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本文編號(hào)：1928350