本文選題：艾滋病　切入點(diǎn)：HAART　出處：《昆明醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的：研究接受HAART治療艾滋病患者出現(xiàn)臨床毒副作用情況與線粒體損傷的動(dòng)態(tài)變化,為艾滋病毒副作用監(jiān)測(cè)和預(yù)警提供理論依據(jù)。 方法：實(shí)驗(yàn)組為昆明市第三人民醫(yī)院門診2011年4月-8月初治的艾滋病患者。對(duì)照組30例為中國科學(xué)院昆明動(dòng)物研究所實(shí)驗(yàn)室研究人員。收集入組患者相關(guān)的一般資料、在治療前和治療后(1月、3月、6月、12月、15月、18月、24月)進(jìn)行相關(guān)實(shí)驗(yàn)室檢查資料：肝功能(ALT、AST)、血液細(xì)胞分析、血乳酸水平、病毒性肝炎、CD4+T淋巴細(xì)胞計(jì)數(shù)、CD8+T淋巴細(xì)胞計(jì)數(shù)及]AART治療方案,通過問診及專科檢查記錄患者藥疹、末梢神經(jīng)炎及脂肪萎縮等情況,并記錄相關(guān)臨床毒副作用出現(xiàn)時(shí)間和治療方案變更情況。同時(shí)提取外周靜脈血全基因組DNA,應(yīng)用Real-time PCR通過雙標(biāo)準(zhǔn)曲線法檢測(cè)線粒體DNA(mtDNA)拷貝數(shù)和損傷率,應(yīng)用普通PCR檢測(cè)線粒體DNA大片段缺失。結(jié)合臨床資料,分析臨床毒副作用情況與線粒體損傷的動(dòng)態(tài)變化,進(jìn)行線粒體損傷相關(guān)高危因素分析。 結(jié)果：共入組73例,死亡率為1.4%,39.7%合并肝炎病毒。22.2%出現(xiàn)臨床毒副作用,最常見的臨床毒副作用為骨髓抑制(12.3%),發(fā)生于3.2±2.1月。其次為肝毒性(11.0%)3.1±2.2月出現(xiàn)、藥疹(5.5%)發(fā)生為1、2、3月、末梢神經(jīng)炎(5.5%)發(fā)生于3、4、7、8月、乳酸酸中毒發(fā)生于8月(1.4%,死亡)和脂肪萎縮發(fā)生于13月(1.4%)。隨著年齡增大,臨床毒副作用發(fā)生率越高。CD4+T淋巴細(xì)胞數(shù)計(jì)數(shù)分別在0-6月、6-12月和12-24月平均上升94.Ocell/μL.44.3cell/μL和34.7cell/μL。靜脈吸毒的HIV/AIDS患者治療后CD4+T淋巴細(xì)胞計(jì)數(shù)上升幅度小于其他傳播途徑的患者。 HIV/AIDS患者在治療前mtDNA拷貝數(shù)為247.37±198.35, mtDNA拷貝數(shù)隨著治療時(shí)間呈遞減趨勢(shì),治療24月mtDNA拷貝數(shù)為154.94±253.12。出現(xiàn)臨床毒副作用的患者mtDNA拷貝數(shù)下降顯著,且發(fā)生臨床毒副作用的患者mtDNA拷貝數(shù)下降顯著高于單純HIV/AIDS患者。治療后mtDNA拷貝數(shù)的下降與肝毒性、末梢神經(jīng)炎、乳酸酸中毒和脂肪萎縮相關(guān),肝毒性患者mtDNA拷貝數(shù)為325.48±24.38的,治療1月mtDNA拷貝數(shù)為263.27±12.11。4例末梢神經(jīng)炎中2例發(fā)生較早的患者mtDNA拷貝數(shù)53.45±32.11,2例發(fā)生時(shí)間較晚的患者mtDNA拷貝數(shù)下降為143.25±41.78。發(fā)生乳酸酸中毒的患者和脂肪萎縮的患者mtDNA拷貝數(shù)分別下降95.23和136.85。老年、合并肝炎病毒感染患者mtDNA拷貝數(shù)顯著下降。2例大片段缺失的患者中,2例出現(xiàn)肝毒性,其中1例合并末梢神經(jīng)炎。線粒體DNA損傷率24月動(dòng)態(tài)隨訪無顯著變化。 結(jié)論：接受HAART治療的艾滋病患者臨床毒副作用發(fā)生率高,是導(dǎo)致患者死亡的重要原因,需密切監(jiān)測(cè)。經(jīng)過HAART治療后,除了骨髓抑制,mtDNA拷貝數(shù)在發(fā)生肝毒性、末梢神經(jīng)炎、乳酸酸中毒和脂肪萎縮之前明顯下降,故可對(duì)其臨床毒副作用發(fā)生進(jìn)行預(yù)警,同時(shí)也是監(jiān)測(cè)線粒體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 鹵2.1 months.The incidence of hepatotoxicity was 3.1 鹵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 鹵1.4 cm) and fat atrophy occurred in 13 months (1.4 鹵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 鹵198.35 before treatment, the mtDNA copy number decreased with the treatment time, and the mtDNA copy number was 154.94 鹵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 鹵24.38.The copy number of mtDNA in 2 patients with peripheral neuritis was 263.27 鹵12.11.4 at one month. The mtDNA copy number of 2 patients with early onset of peripheral neuritis was 53.45 鹵32.110.The mtDNA copy number of 2 patients with late onset time decreased to 143.25 鹵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.
【學(xué)位授予單位】：昆明醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R512.91

【參考文獻(xiàn)】

相關(guān)期刊論文 前8條

1 鄭煜煌;周華英;何艷;鄧曉軍;朱章萍;符政遠(yuǎn);申紅連;王建國;王為德;文森;黎雪峰;鄭力文;;艾滋病7年高效抗逆轉(zhuǎn)錄病毒治療的多中心前瞻性觀察[J];中國感染控制雜志;2010年05期

2 王行;王惠民;;實(shí)時(shí)定量PCR技術(shù)的方法學(xué)分類[J];臨床檢驗(yàn)雜志;2007年01期

3 陽成波,印遇龍,黃瑞林,李鐵軍,單計(jì)光,唐志如;實(shí)時(shí)定量RT-PCR的原理及方法[J];免疫學(xué)雜志;2003年S1期

4 余惠芬;賈曼紅;韓瑜;安曉靜;徐諾雅;張小波;馬艷玲;張勇;;云南省HIV感染人群應(yīng)對(duì)艾滋病的現(xiàn)狀分析[J];中華疾病控制雜志;2012年12期

5 唐永凱;賈永義;;熒光定量PCR數(shù)據(jù)處理方法的探討[J];生物技術(shù);2008年03期

6 徐麗華;劉春雷;常玉梅;梁利群;劉金亮;高國強(qiáng);韓啟霞;;雙標(biāo)準(zhǔn)曲線相對(duì)定量PCR試驗(yàn)原理與方法[J];生物技術(shù)通報(bào);2011年01期

7 金永梅;白勁松;李玉葉;劉俊;陳建華;于敏;田波;;HIV/AIDS合并藥疹患者實(shí)驗(yàn)室資料和預(yù)后的相關(guān)性研究[J];皮膚病與性病;2013年06期

8 謝靜;李太生;;艾滋病抗病毒治療新藥的研究進(jìn)展[J];中國艾滋病性病;2008年06期

，

本文編號(hào)：1707845