Department of Dermatology, Massachusetts General Hospital (MGH), Harvard Medical School (HMS), Boston, MA, USA.
Immunobiology. 2013 Apr;218(4):620-7. doi: 10.1016/j.imbio.2012.07.030. Epub 2012 Aug 4.
An altered redox status and increased lymphocyte apoptosis have been implicated in the development of systemic lupus erythematosus (SLE). In this study, we evaluated the relationship between glutathione (GSH) depletion, reactive oxygen species (ROS) and, the progression of apoptosis and their association with SLE severity. Significant low levels of intracellular glutathione, total thiol and altered redox state (GSH/GSSG) were found in SLE patients, in which lymphocyte apoptosis and activated caspase-3 expression in the lymphocytes were remarkably increased. The severity of disease was positively allied with the increased levels of lymphocyte apoptosis and caspase-3, but negatively with the decreased levels of total thiol, depleted intracellular glutathione and altered redox state (GSH/GSSG). The lymphocyte apoptosis and activated caspase-3 expression were negatively associated with intracellular levels of GSH and redox state and positively associated with the elevated levels of multiple oxidative stress markers; ROS and lipid peroxidation measured as malondialdehyde (MDA). These results suggest that GSH depletion and elevated oxidative stress trigger apoptosis and may be coupled with the severity of the disease.
氧化还原状态的改变和淋巴细胞凋亡的增加与系统性红斑狼疮（SLE）的发展有关。在这项研究中，我们评估了谷胱甘肽（GSH）耗竭、活性氧（ROS）与凋亡进展之间的关系，以及它们与 SLE 严重程度的关联。我们发现 SLE 患者的细胞内谷胱甘肽、总巯基和氧化还原状态（GSH/GSSG）明显降低，淋巴细胞凋亡和淋巴细胞中激活的 caspase-3 表达显著增加。疾病的严重程度与淋巴细胞凋亡和 caspase-3 的增加呈正相关，而与总巯基、细胞内谷胱甘肽耗竭和氧化还原状态（GSH/GSSG）降低呈负相关。淋巴细胞凋亡和激活的 caspase-3 表达与细胞内 GSH 水平和氧化还原状态呈负相关，与多种氧化应激标志物（ROS 和丙二醛（MDA）等脂质过氧化产物）水平升高呈正相关。这些结果表明，GSH 耗竭和氧化应激升高可引发细胞凋亡，并可能与疾病的严重程度有关。
