脂联素和超敏C反应蛋白在HIV感染者抗反转录病毒治疗中的变化

发布时间：2018-07-23 17:11

【摘要】：高效反转录病毒治疗（the highly active antiretroviral therapy, HAART）大大降低了与人类免疫缺陷病毒（human immunodeficiency virus, HIV）感染相关的死亡率和发病率，延长了患者预期寿命。然而， HAART的长期副作用，如心血管疾病（cardiovascular disease, CVD），又成为治疗HIV感染者医生新的挑战[1]。据报道，HIV感染者的CVD发病率至少是普通人群的3倍[2]。而且，世界卫生组织预言，，到2030年，HIV/AIDS和CVD将位于全球死亡率的前3位[3]。但是，HIV感染者CVD的评估还比较少，现有文献观点也不一致，且互相矛盾[1]。因此，HIV感染并发CVD的防治成为AIDS研究最关注的领域之一。据目前研究现状分析，评估HIV感染、HAART治疗及CVD危险性之间相互联系的策略可以采用直接法，也可以采用间接法。直接法就是在大量人群中比较急性心肌梗死（myocardial infarction, MI）发病率或颈动脉内膜中层厚度（carotidintima-media thickness, C-IMT）。而间接法则是通过CVD的危险因素和标志物来间接地评估它们之间的关系[4]。例如，脂联素（adiponectin, APN）和超敏C反应蛋白（high-sensitivity C-reactive protein, hs-CRP）就是两个重要CVD标志物，二者具有很高的临床及科研价值。所以我们在实验中研究了APN和hs-CRP的变化规律，以便为及早评估HIV/AIDS人群心血管疾病状况提供实验依据。主要研究方法和内容： 1. APN在抗反转录病毒治疗中的变化实验（一）首先将研究对象的静脉血离心后吸取血浆，采用酶联免疫吸附试验（in-house enzyme-linked immunosorbent assays, ELISA）测定血浆中的APN浓度。按照横向研究和纵向研究的设计，观察HIV/AIDS人群APN的特点及在时间上的变化规律，为后续实验及分析提供操作经验和相关数据。 2. hs-CRP在抗反转录病毒治疗中的变化实验（二）将研究对象的静脉血离心后吸取血浆，采用ELISA技术测定血浆中的hs-CRP浓度，按照横向研究和纵向研究的设计，观察HIV/AIDS人群hs-CRP的特点及在时间上的变化规律，为后续分析提供相关数据。 3. CD4+T淋巴细胞在抗反转录病毒治疗中的变化实验（三）采集研究对象的静脉血后24小时内用BD FACS Calibur流式细胞仪检测CD4+T淋巴细胞数，通过横向和纵向比较观察HIV/AIDS人群CD4+T淋巴细胞数量的特点及在时间上的变化规律，为后续分析提供相关数据。主要研究结果： 1.我们发现，治疗组APN浓度（3.35±3.21μg/ml）明显低于未治疗组（6.34±6.93μg/ml）和对照组（5.34±5.44μg/ml）。在随访中，APN于12周、24周前逐渐上升，36周后下降，到48周、60周时下降明显，呈先升后降的变化趋势。 2. hs-CRP检测结果三组之间没有差异。随访中发现hs-CRP浓度虽然在HAART治疗过程中有逐渐下降的变化，但是这种变化并没有统计学差异。 3.治疗组CD4+T淋巴细胞数（350.2±149.5个/μL）明显高于未治疗组（234.5±149.5个/μL）。CD4+T淋巴细胞在随访中较HAART治疗前升高。 4.和治疗前相比较，总胆固醇（total cholesterol, TC）从12周以后、甘油三脂(triglycerides, TG)从48周以后、低密度脂蛋白(low-density lipoprotein cholesterol,LDL)从24周以后开始出现明显的升高。结论：我们发现，在接受HAART治疗的HIV感染者当中，APN在HAART治疗中先升高后逐渐降低，TC、TG和LDL逐渐升高，hs-CRP没有明显改变，因低脂联素血症、血脂异常是CVD的危险因素，所以动态监测这些指标对HIV感染者CVD的早期预防是有利的。
[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.
【学位授予单位】：第四军医大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R512.91

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