【摘要】：高效反轉(zhuǎn)錄病毒治療（the highly active antiretroviral therapy, HAART）大大降低了與人類免疫缺陷病毒（human immunodeficiency virus, HIV）感染相關(guān)的死亡率和發(fā)病率，延長了患者預(yù)期壽命。然而， HAART的長期副作用，如心血管疾�。╟ardiovascular disease, CVD），又成為治療HIV感染者醫(yī)生新的挑戰(zhàn)[1]。據(jù)報道，HIV感染者的CVD發(fā)病率至少是普通人群的3倍[2]。而且，世界衛(wèi)生組織預(yù)言，，到2030年，HIV/AIDS和CVD將位于全球死亡率的前3位[3]。但是，HIV感染者CVD的評估還比較少，現(xiàn)有文獻觀點也不一致，且互相矛盾[1]。因此，HIV感染并發(fā)CVD的防治成為AIDS研究最關(guān)注的領(lǐng)域之一。 據(jù)目前研究現(xiàn)狀分析，評估HIV感染、HAART治療及CVD危險性之間相互聯(lián)系的策略可以采用直接法，也可以采用間接法。直接法就是在大量人群中比較急性心肌梗死（myocardial infarction, MI）發(fā)病率或頸動脈內(nèi)膜中層厚度（carotidintima-media thickness, C-IMT）。而間接法則是通過CVD的危險因素和標志物來間接地評估它們之間的關(guān)系[4]。例如，脂聯(lián)素（adiponectin, APN）和超敏C反應(yīng)蛋白（high-sensitivity C-reactive protein, hs-CRP）就是兩個重要CVD標志物，二者具有很高的臨床及科研價值。所以我們在實驗中研究了APN和hs-CRP的變化規(guī)律，以便為及早評估HIV/AIDS人群心血管疾病狀況提供實驗依據(jù)。 主要研究方法和內(nèi)容： 1. APN在抗反轉(zhuǎn)錄病毒治療中的變化 實驗（一）首先將研究對象的靜脈血離心后吸取血漿，采用酶聯(lián)免疫吸附試驗（in-house enzyme-linked immunosorbent assays, ELISA）測定血漿中的APN濃度。按照橫向研究和縱向研究的設(shè)計，觀察HIV/AIDS人群APN的特點及在時間上的變化規(guī)律，為后續(xù)實驗及分析提供操作經(jīng)驗和相關(guān)數(shù)據(jù)。 2. hs-CRP在抗反轉(zhuǎn)錄病毒治療中的變化 實驗（二）將研究對象的靜脈血離心后吸取血漿，采用ELISA技術(shù)測定血漿中的hs-CRP濃度，按照橫向研究和縱向研究的設(shè)計，觀察HIV/AIDS人群hs-CRP的特點及在時間上的變化規(guī)律，為后續(xù)分析提供相關(guān)數(shù)據(jù)。 3. CD4+T淋巴細胞在抗反轉(zhuǎn)錄病毒治療中的變化 實驗（三）采集研究對象的靜脈血后24小時內(nèi)用BD FACS Calibur流式細胞儀檢測CD4+T淋巴細胞數(shù)，通過橫向和縱向比較觀察HIV/AIDS人群CD4+T淋巴細胞數(shù)量的特點及在時間上的變化規(guī)律，為后續(xù)分析提供相關(guān)數(shù)據(jù)。 主要研究結(jié)果： 1.我們發(fā)現(xiàn)，治療組APN濃度（3.35±3.21μg/ml）明顯低于未治療組（6.34±6.93μg/ml）和對照組（5.34±5.44μg/ml）。在隨訪中，APN于12周、24周前逐漸上升，36周后下降，到48周、60周時下降明顯，呈先升后降的變化趨勢。 2. hs-CRP檢測結(jié)果三組之間沒有差異。隨訪中發(fā)現(xiàn)hs-CRP濃度雖然在HAART治療過程中有逐漸下降的變化，但是這種變化并沒有統(tǒng)計學差異。 3.治療組CD4+T淋巴細胞數(shù)（350.2±149.5個/μL）明顯高于未治療組（234.5±149.5個/μL）。CD4+T淋巴細胞在隨訪中較HAART治療前升高。 4.和治療前相比較，總膽固醇（total cholesterol, TC）從12周以后、甘油三脂(triglycerides, TG)從48周以后、低密度脂蛋白(low-density lipoprotein cholesterol,LDL)從24周以后開始出現(xiàn)明顯的升高。 結(jié)論： 我們發(fā)現(xiàn)，在接受HAART治療的HIV感染者當中，APN在HAART治療中先升高后逐漸降低，TC、TG和LDL逐漸升高，hs-CRP沒有明顯改變，因低脂聯(lián)素血癥、血脂異常是CVD的危險因素，所以動態(tài)監(jiān)測這些指標對HIV感染者CVD的早期預(yù)防是有利的。
[Abstract]:High performance retrovirus therapy (the highly active antiretroviral therapy, HAART) greatly reduces mortality and morbidity associated with human immunodeficiency virus (human immunodeficiency virus, HIV) infection and prolongs patient life expectancy. However, HAART long-term side effects such as cardiovascular disease (cardiovascular,), [1]., a new challenge for HIV infection doctors, reports that the incidence of CVD in HIV infected people is at least 3 times as high as [2]. in the general population, and the WHO predicts that by 2030, HIV/AIDS and CVD will be located at the top 3 [3]. of the global mortality rate, but the CVD of the HIV infected persons is still less, and the existing literature views are inconsistent and mutually exclusive. Contradictory [1]., therefore, prevention and treatment of HIV infection complicated with CVD has become one of the most concerned areas in AIDS research.
According to current research status analysis, the strategy of assessing the relationship between HIV infection, HAART treatment and CVD risk can be used directly and indirectly. The direct method is to compare the incidence of acute myocardial infarction (myocardial infarction, MI) or the intima media thickness of carotid artery (carotidintima-media thickness, MI) in a large number of people. C-IMT). The indirect principle is to indirectly evaluate their relationship through CVD's risk factors and markers, [4]., for example, adiponectin (APN) and hypersensitive C reactive protein (high-sensitivity C-reactive protein, hs-CRP) are two important CVD markers, and the two are of high clinical and scientific value. So we are in reality The change rules of APN and hs-CRP were studied in order to provide experimental evidence for early assessment of cardiovascular disease in HIV/AIDS population.
Main research methods and contents:
1. APN changes in antiretroviral therapy
The experiment (1) first, the venous blood of the subjects was centrifuged and plasma was absorbed. The concentration of APN in plasma was measured by in-house enzyme-linked immunosorbent assays (ELISA). According to the design of horizontal and longitudinal studies, the characteristics and time changes of APN in HIV/AIDS population were observed and the follow-up experiments were conducted. And the analysis provides operational experience and related data.
2. hs-CRP changes in antiretroviral therapy
In the experiment (two) the venous blood of the subjects was centrifuged and plasma was drawn after centrifugation. The concentration of hs-CRP in the plasma was measured by ELISA technique. According to the design of horizontal and longitudinal studies, the characteristics of hs-CRP in the HIV/AIDS population and the changes in the time were observed, and the related data were provided for the follow-up analysis.
Changes of 3. CD4+T lymphocytes in antiretroviral therapy
In the experiment (three) the number of CD4+T lymphocytes was detected by BD FACS Calibur flow cytometry within 24 hours after the venous blood collection of the subjects. The characteristics of the number of CD4+T lymphocytes in the HIV/AIDS population were compared and the changes in the time were observed through the transverse and longitudinal comparison, and the relevant data were provided for the follow-up analysis.
The main research results are as follows:
1. we found that the concentration of APN (3.35 + 3.21 mu g/ml) in the treatment group was significantly lower than that in the untreated group (6.34 + 6.93 micron g/ml) and the control group (5.34 + 5.44 g/ml). During the follow-up, APN increased gradually at 12 weeks, 24 weeks ago, and declined after 36 weeks, to 48 weeks, and decreased markedly in 60 weeks, showing a trend of first rise and then descend.
There was no difference between the three groups of the 2. hs-CRP test results. There was a gradual decrease in the concentration of hs-CRP during the follow-up of HAART treatment, but there was no statistical difference in this change.
3. the number of CD4+T lymphocytes (350.2 + 149.5 / mu L) in the treatment group was significantly higher than that in the untreated group (234.5 + 149.5 / u L).CD4+T lymphocyte in the follow-up period, which was higher than before the HAART treatment.
4. compared with before treatment, total cholesterol (total cholesterol, TC) from 12 weeks later, glycerin three fat (triglycerides, TG) from 48 weeks later, low density lipoprotein (low-density lipoprotein cholesterol, LDL) began to appear significantly after 24 weeks.
Conclusion:
We found that in the HIV infected people receiving HAART treatment, APN increased gradually in the HAART treatment and gradually decreased, TC, TG and LDL increased gradually, and hs-CRP did not change obviously. Because of Hypolipidemia, dyslipidemia was a risk factor for CVD, so dynamic monitoring of these indicators was beneficial to the early prevention of CVD in HIV infected persons.
【學位授予單位】：第四軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2013
【分類號】：R512.91

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