CAJ | 학술논문

目的：探讨 PBMC 线粒体毒性相关指标在监测艾滋病 HAART 过程中线粒体毒性的意义。方法选取线粒体 DNA（mtDNA）、线粒体胸苷激酶（TK2）和依赖 p53的核苷酸还原酶小亚基2（p53R2）为线粒体毒性检测指标，应用荧光定量实时 PCR 技术，观察22例接受以司他夫定（齐多夫定）＋拉米夫定为骨干 HAART 方案的艾滋病患者治疗前、治疗后48及96周 PBMC 中 mtDNA、TK2和p53R2表达水平的变化。组间比较采用独立样本 t 检验。结果艾滋病患者接受 HAART 前 PBMC 中mtDNA 相对表达量为3．27±0．94，治疗48及96周表达量分别为2．16±0．85和1．66±0．66，与治疗前比较差异均有统计学意义（t 值分别为－3．90和－6．29，均 P ＜0．01）；TK2相对表达水平治疗前为0．37±0．13，治疗48及96周分别为1．01±0．25及2．13±0．61，治疗前与治疗48、96周，以及治疗48周与96周比较，差异均有统计学意义（t 值分别为10．77、8．00和3．56，均 P ＜0．01）；p53R2水平治疗前为0．86±0．39，治疗48及96周分别为2．36±1．14和7．73±0．65，治疗前与治疗48、96周，以及治疗48周与96周比较，差异均有统计学意义（t 值分别为3．27、12．26和13．25，均 P ＜0．01）。结论艾滋病患者HAART 过程中 PBMC 线粒体毒性相关指标 mtDNA、TK2及 p53R2发生明显变化，可作为线粒体损害的监测指标。
목적：탐토 PBMC 선립체독성상관지표재감측애자병 HAART 과정중선립체독성적의의。방법선취선립체 DNA（mtDNA）、선립체흉감격매（TK2）화의뢰 p53적핵감산환원매소아기2（p53R2）위선립체독성검측지표，응용형광정량실시 PCR 기술，관찰22례접수이사타부정（제다부정）＋랍미부정위골간 HAART 방안적애자병환자치료전、치료후48급96주 PBMC 중 mtDNA、TK2화p53R2표체수평적변화。조간비교채용독립양본 t 검험。결과애자병환자접수 HAART 전 PBMC 중mtDNA 상대표체량위3．27±0．94，치료48급96주표체량분별위2．16±0．85화1．66±0．66，여치료전비교차이균유통계학의의（t 치분별위－3．90화－6．29，균 P ＜0．01）；TK2상대표체수평치료전위0．37±0．13，치료48급96주분별위1．01±0．25급2．13±0．61，치료전여치료48、96주，이급치료48주여96주비교，차이균유통계학의의（t 치분별위10．77、8．00화3．56，균 P ＜0．01）；p53R2수평치료전위0．86±0．39，치료48급96주분별위2．36±1．14화7．73±0．65，치료전여치료48、96주，이급치료48주여96주비교，차이균유통계학의의（t 치분별위3．27、12．26화13．25，균 P ＜0．01）。결론애자병환자HAART 과정중 PBMC 선립체독성상관지표 mtDNA、TK2급 p53R2발생명현변화，가작위선립체손해적감측지표。
Objective To explore whether the mitochondrial toxicity markers of peripheral blood mononuclear cells (PBMC)are of significance in monitoring mitochondrial toxicity during highly active antiretroviral therapy (HAART)in patients with acquired immune deficiency syndrome (AIDS).Methods Mitochondrial DNA (mtDNA),mitochondrial thymidine kinase (TK2 )and p53-inducible ribonucleotide reductase small subunit 2 (p53R2 )were selected as mitochondrial toxicity markers.The expression changes of theses markers of PBMC in 22 AIDS patients were detected by real time quantitative polymerase chain reaction (q-PCR)at baseline,48 weeks and 96 weeks after initiation of the treatment. All the patients received stavudine/zidovudine and lamivudine as the mainstay of the HAART regimen. Independent-samples t test was used.Results The relative expression level of mtDNA in patients before HAART was 3.27 ± 0.94,and decreased to 2.16±0.85 at week 48 and 1 .66±0.66 at week 96, respectively.The differences were both significant compared with the level prior to the treatment (t =-3.90,P <0.01 and t =-6.29,P <0.01 ,respectively).The relative expression level of TK2 before HAART was 0.37 ±0.13,and increased to 1 .01 ±0.25 at week 48 and 2.13 ±0.61 at week 96 of the treatment.After pairwise comparisons of the three pairs of data (pre-HAART vs week 48 of the treatment,pre-HAART vs week 96 of the treatment and week 48 vs week 96 of the treatment),the differences were all significant (t = 10.77,8.00 and 3.56,respectively;all P < 0.01 ).The relative expression level of p53R2 was 0.86±0.39 before HAART,but gradually increased to 2.36 ±1 .14 and 7.73±0.65 ,respectively,at week 48 and week 96 of the treatment.The differences in p53R2 levels among three groups after pairwise comparison were all significant (t=3.27,12.26 and 13.25,respectively;all P < 0.01 ).Conclusions The expression levels of mtDNA,TK2 and p53R2 in PBMC could change significantly during HAART in AIDS patients,which might be used as indexes for monitoring mitochondrial toxicity.