艾滋病患者HAART相关临床毒副作用与线粒体损伤动态研究

发布时间：2018-04-04 01:51

本文选题：艾滋病　切入点：HAART　出处：《昆明医科大学》2014年硕士论文

【摘要】：目的：研究接受HAART治疗艾滋病患者出现临床毒副作用情况与线粒体损伤的动态变化,为艾滋病毒副作用监测和预警提供理论依据。方法：实验组为昆明市第三人民医院门诊2011年4月-8月初治的艾滋病患者。对照组30例为中国科学院昆明动物研究所实验室研究人员。收集入组患者相关的一般资料、在治疗前和治疗后(1月、3月、6月、12月、15月、18月、24月)进行相关实验室检查资料：肝功能(ALT、AST)、血液细胞分析、血乳酸水平、病毒性肝炎、CD4+T淋巴细胞计数、CD8+T淋巴细胞计数及]AART治疗方案,通过问诊及专科检查记录患者药疹、末梢神经炎及脂肪萎缩等情况,并记录相关临床毒副作用出现时间和治疗方案变更情况。同时提取外周静脉血全基因组DNA,应用Real-time PCR通过双标准曲线法检测线粒体DNA(mtDNA)拷贝数和损伤率,应用普通PCR检测线粒体DNA大片段缺失。结合临床资料,分析临床毒副作用情况与线粒体损伤的动态变化,进行线粒体损伤相关高危因素分析。结果：共入组73例,死亡率为1.4%,39.7%合并肝炎病毒。22.2%出现临床毒副作用,最常见的临床毒副作用为骨髓抑制(12.3%),发生于3.2±2.1月。其次为肝毒性(11.0%)3.1±2.2月出现、药疹(5.5%)发生为1、2、3月、末梢神经炎(5.5%)发生于3、4、7、8月、乳酸酸中毒发生于8月(1.4%,死亡)和脂肪萎缩发生于13月(1.4%)。随着年龄增大,临床毒副作用发生率越高。CD4+T淋巴细胞数计数分别在0-6月、6-12月和12-24月平均上升94.Ocell/μL.44.3cell/μL和34.7cell/μL。静脉吸毒的HIV/AIDS患者治疗后CD4+T淋巴细胞计数上升幅度小于其他传播途径的患者。 HIV/AIDS患者在治疗前mtDNA拷贝数为247.37±198.35, mtDNA拷贝数随着治疗时间呈递减趋势,治疗24月mtDNA拷贝数为154.94±253.12。出现临床毒副作用的患者mtDNA拷贝数下降显著,且发生临床毒副作用的患者mtDNA拷贝数下降显著高于单纯HIV/AIDS患者。治疗后mtDNA拷贝数的下降与肝毒性、末梢神经炎、乳酸酸中毒和脂肪萎缩相关,肝毒性患者mtDNA拷贝数为325.48±24.38的,治疗1月mtDNA拷贝数为263.27±12.11。4例末梢神经炎中2例发生较早的患者mtDNA拷贝数53.45±32.11,2例发生时间较晚的患者mtDNA拷贝数下降为143.25±41.78。发生乳酸酸中毒的患者和脂肪萎缩的患者mtDNA拷贝数分别下降95.23和136.85。老年、合并肝炎病毒感染患者mtDNA拷贝数显著下降。2例大片段缺失的患者中,2例出现肝毒性,其中1例合并末梢神经炎。线粒体DNA损伤率24月动态随访无显著变化。结论：接受HAART治疗的艾滋病患者临床毒副作用发生率高,是导致患者死亡的重要原因,需密切监测。经过HAART治疗后,除了骨髓抑制,mtDNA拷贝数在发生肝毒性、末梢神经炎、乳酸酸中毒和脂肪萎缩之前明显下降,故可对其临床毒副作用发生进行预警,同时也是监测线粒体毒性安全可靠的方法。
[Abstract]:Objective: to study the dynamic changes of clinical side effects and mitochondrial damage in AIDS patients treated with HAART, and to provide theoretical basis for monitoring and warning of AIDS side effects.Methods: the experimental group was treated with AIDS from April to early August 2011 in the outpatient department of the third people's Hospital of Kunming.The control group (n = 30) was a laboratory researcher of Kunming Institute of Zoology, Chinese Academy of Sciences.The relevant general data of the patients were collected and the relevant laboratory data were collected before and after treatment (January, March, June, December, 15, 18, 24 months): liver function, blood cell analysis, blood lactic acid level.CD 4 T lymphocyte count and CD8 T lymphocyte count in viral hepatitis A AART treatment program was used to record the drug eruption, peripheral neuritis and fat atrophy.The time of occurrence of clinical side effects and the changes of treatment plan were recorded.At the same time, the whole genomic DNA of peripheral venous blood was extracted. The copy number and damage rate of mitochondrial PCR were detected by double standard curve method by Real-time PCR, and the deletion of large mitochondrial DNA fragment was detected by ordinary PCR.Combined with clinical data, the dynamic changes of clinical toxic side effects and mitochondrial damage were analyzed, and the high risk factors of mitochondrial injury were analyzed.Results: there were 73 cases in the group, the mortality rate was 1.4% and 39.7% with hepatitis virus. 22.2% had clinical side effects. The most common clinical side effects were bone marrow suppression 12.3T, which occurred in 3.2 卤2.1 months.The incidence of hepatotoxicity was 3.1 卤2.2 months, and the incidence of drug eruption was 5.5%. In 3 months, the peripheral neuritis occurred at 5.5%. In August, lactic acidosis occurred in August (1.4%, death) and fat atrophy occurred in 13 months (1.4%) and atrophied in 13 months (1.4 卤1.4 cm) and fat atrophy occurred in 13 months (1.4 卤1.4 cm).With the increase of age, the incidence of clinical side effects increased. The number of CD4 T lymphocytes increased from 0 to 6 months, from June to December, and from December to December, and from December to December, respectively, and increased 94.Ocell/ 渭 L.44.3cell/ 渭 L and 34.7cell/ 渭 L, respectively.The increase of CD4 T lymphocyte count in HIV/AIDS patients with intravenous drug abuse was lower than that in patients with other transmission routes.The mtDNA copy number of HIV/AIDS patients was 247.37 卤198.35 before treatment, the mtDNA copy number decreased with the treatment time, and the mtDNA copy number was 154.94 卤253.12 months after 24 months treatment.The number of mtDNA copies in patients with clinical side effects decreased significantly, and the number of copies of mtDNA in patients with clinical side effects was significantly lower than that in patients with simple HIV/AIDS.The decrease of mtDNA copy number after treatment was associated with hepatotoxicity, peripheral neuritis, lactic acidosis and fat atrophy. The mtDNA copy number of patients with hepatotoxicity was 325.48 卤24.38.The copy number of mtDNA in 2 patients with peripheral neuritis was 263.27 卤12.11.4 at one month. The mtDNA copy number of 2 patients with early onset of peripheral neuritis was 53.45 卤32.110.The mtDNA copy number of 2 patients with late onset time decreased to 143.25 卤41.78.The number of mtDNA copies in patients with lactic acidosis and those with fat atrophy decreased 95.23 and 136.85, respectively.In elderly patients with hepatitis virus infection, the mtDNA copy number decreased significantly in 2 out of 2 patients with large fragment deletion, including 1 patient with peripheral neuritis.There was no significant change in mitochondrial DNA damage rate during 24 months follow-up.Conclusion: AIDS patients treated with HAART have high incidence of clinical toxicity and side effects, which is an important cause of death and should be closely monitored.After HAART treatment, the copy number of mtDNA decreased significantly before the occurrence of hepatotoxicity, peripheral neuritis, lactic acidosis and fat atrophy, in addition to bone marrow suppression.It is also a safe and reliable method for monitoring mitochondrial toxicity.
【学位授予单位】：昆明医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R512.91

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