线粒体DNA含量与HIV相关脂肪营养不良的关系

Association between the change regularity of peripheral blood mononuclear cell mitochondrial deoxyribonucleic acid content and human immunodeficiency virus-related lipodystrophy

目的研究高效联合抗反转录病毒治疗（HAART）过程中外周血单核淋巴细胞（PBMC）内线粒体DNA（mtDNA）含量变化规律及其与人类免疫缺陷病毒（HIV）感染相关脂肪营养不良（HIV．LD）的相关性。方法通过实时定量PCR（real—timePCR），对2002年5月至2008年5月北京协和医院感染内科门诊长期规律随访的33例HIV／AIDS中国成年患者抗病毒治疗基线、半年、2年的mtDNA含量测定，其中出现了HIV—LD的为17例，比较各组间的差异。结果HIV／AIDS患者治疗基线PBMC mtDNA含量低于健康对照组（9．578比17．195，P〈0．01）。HIV—LD组治疗各时点PBMCmtDNA含量均显著低于未出现脂肪营养不良综合征（NLD）组（治疗基线、治疗半年、治疗2年分别为13．619比5．775、6．360比1．387、7．170比1．266）。mtDNA含量降低先于临床HIV—LD的出现。使用司他夫定（d4T）方案组患者PBMCmtDNA含量（2^-△△C1）治疗后较基线显著降低，而齐多夫定（AZT）方案组患者治疗前后PBMC mtDNA含量变化不显著（P=0．205）。结论HIV感染和d4T与PBMCmtDNA含量的下降具有密切关系。

Objective To investigate the change regularity of peripheral blood mononuclear cell （PBMC） mtDNA （mitochondrial deoxyribonucleic acid ）content and its association with HIV-LD （human immunodeficiency virus-related lipodystrophy） in HAART （ highly active antiretroviral therapy）. Methods At baseline, Months 6 and 24 of therapy, the myopreserved PBMC were collected from 33 patients on a regular follow-up at our clinic. Among them, 17 had HIV-LD. Then total DNA was extracted and mtDNA content quantified by real-time PCR （polymerase chain reaction）. Results The HIV/AIDS patients had a lower content of PBMC mtDNA （2^-△△C1） than the healthy controls at baseline （9. 578 vs 17. 195, P 〈 0. 01 ）. The mtDNA content was lower in the HIV-LD group than that in the no LD （NLD） group at each timepoint of therapy （ 13. 619 vs 5. 775, 6. 360 vs 1. 387, 7. 170 vs 1. 266, all P 〈0. 05）. In the HIV-LD group, the half- and 2-year PBMC mtDNA content was markedly lower than those at baseline （ both P 〈 0. 05 ）. And the change of mtDNA content （ within half a year） was earlier than the onset of clinical HIV-LD at one year later. In the NLD group, the PBMC mtDNA content have an insignificant change after therapy. The mtDNA content decreased significantly in stavudine （d4T）-containing regimen group after treatment （P 〈 0.01 ）, but showed no significant change in zidovudine （AZT） -containing regimen group after therapy. Conclusion The decreased content of PBMC mtDNA after HIV infection and during HAART therapy is associated with HIV-LD. Nueleoside reverse transcriptase inhibitor, especially d4T, plays an important role in the progression of HIV-LD.