Watson Walter H, Ritzenthaler Jeffrey D, Peyrani Paula, Wiemken Timothy L, Furmanek Stephen, Reyes Vega Andrea M, Burke Tom J, Zheng Yuxuan, Ramirez Julio A, Roman Jesse
Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, USA; Department of Pharmacology & Toxicology, University of Louisville School of Medicine, USA.
Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, University of Louisville School of Medicine, USA.
Free Radic Biol Med. 2019 Nov 1;143:55-61. doi: 10.1016/j.freeradbiomed.2019.07.031. Epub 2019 Jul 29.
Chronic obstructive pulmonary disease (COPD) is prevalent in patients infected with HIV. The purpose of this study was to test the hypothesis that systemic oxidation correlates with loss of lung function in subjects with COPD, and that HIV infection can contribute to creating such an environment. Subjects were recruited at the University of Louisville in the following groups: HIV-infected (n = 36), COPD (n = 32), HIV and COPD (n = 28), and uninfected controls with normal lung function (n = 34). HIV infection was assessed by viral load and CD4 cell counts. Pulmonary function was determined by spirometry, and plasma was collected for measurement of cysteine (Cys), cystine (CySS), glutathione (GSH) and GSH disulfide (GSSG) by HPLC followed by estimation of redox potentials (E) using the Nernst equation. Results showed that patients with COPD had more oxidized plasma E Cys/CySS than patients with normal lung function, but plasma E GSH/GSSG was unaltered. In addition, there was a correlation between the extent of plasma E Cys/CySS oxidation and loss of lung function, and this correlation remained even after correcting for age, sex, race and body mass index. HIV infection per se was not associated with increased oxidation of plasma E Cys/CySS, but plasma E Cys/CySS was more oxidized in patients with lower CD4-positve T cell counts. In patients with both HIV infection and COPD, there was a significant correlation between CD4 cell counts and lung function. Thus, systemic oxidation correlated with decreased lung function in subjects with COPD and decreased CD4 counts in subjects infected with HIV. Thus, factors contributing to plasma E Cys/CySS may represent novel mechanisms underlying the increased prevalence of COPD in people living with HIV.
慢性阻塞性肺疾病(COPD)在感染HIV的患者中很常见。本研究的目的是检验以下假设:全身氧化与COPD患者肺功能丧失相关,且HIV感染会促使这种环境的形成。在路易斯维尔大学招募了以下几组受试者:HIV感染组(n = 36)、COPD组(n = 32)、HIV合并COPD组(n = 28)以及肺功能正常的未感染对照组(n = 34)。通过病毒载量和CD4细胞计数评估HIV感染情况。通过肺活量测定法确定肺功能,并采集血浆,采用高效液相色谱法测量半胱氨酸(Cys)、胱氨酸(CySS)、谷胱甘肽(GSH)和谷胱甘肽二硫化物(GSSG),随后使用能斯特方程估算氧化还原电位(E)。结果显示,与肺功能正常的患者相比,COPD患者血浆中E Cys/CySS的氧化程度更高,但血浆E GSH/GSSG未发生改变。此外,血浆E Cys/CySS的氧化程度与肺功能丧失之间存在相关性,即使在校正年龄、性别、种族和体重指数后,这种相关性依然存在。HIV感染本身与血浆E Cys/CySS氧化增加无关,但CD4阳性T细胞计数较低的患者血浆E Cys/CySS的氧化程度更高。在同时感染HIV和患有COPD的患者中,CD4细胞计数与肺功能之间存在显著相关性。因此,全身氧化与COPD患者肺功能下降以及HIV感染患者CD4计数下降相关。因此,导致血浆E Cys/CySS的因素可能代表了HIV感染者中COPD患病率增加的潜在新机制。