Waslo Carin, Bourdette Dennis, Gray Nora, Wright Kirsten, Spain Rebecca
Veterans Affairs Portland Health Care System, Portland, OR, USA.
Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road - L226, Portland, OR, 97239, USA.
Curr Treat Options Neurol. 2019 May 6;21(6):26. doi: 10.1007/s11940-019-0566-1.
Oxidative stress (OS), when oxidative forces outweigh endogenous and nutritional antioxidant defenses, contributes to the pathophysiology of multiple sclerosis (MS). Evidence of OS is found during acute relapses, in active inflammatory lesions, and in chronic, longstanding plaques. OS results in both ongoing inflammation and neurodegeneration. Antioxidant therapies are a rational strategy for people with MS with all phenotypes and disease durations. PURPOSE OF REVIEW: To understand the function of OS in health and disease, to examine the contributions of OS to MS pathophysiology, and to review current evidence for the effects of selected antioxidant therapies in people with MS (PwMS) with a focus on lipoic acid (LA). RECENT FINDINGS: Studies of antioxidant interventions in both animal and in vivo models result in reductions in serum markers of OS and increases in levels and activity of antioxidant enzymes. Antioxidant trials in PwMS, while generally underpowered, detect short-term improvements in markers of OS and antioxidant defenses, and to a lesser extent, in clinical symptoms (fatigue, depression). The best evidence to date is a 2-year trial of LA in secondary progressive MS which demonstrated a significant reduction of whole-brain atrophy and trend toward improvement in walking speed. Antioxidant therapy is a promising approach to treat MS across the spectrum and duration of disease. Rigorous and well-powered trials are needed to determine their therapeutic benefits.
氧化应激（OS），即氧化力超过内源性和营养性抗氧化防御能力时，会导致多发性硬化症（MS）的病理生理过程。在急性复发期、活动性炎症病灶以及慢性、长期存在的斑块中均发现了氧化应激的证据。氧化应激会导致持续的炎症和神经退行性变。抗氧化疗法对于所有表型和病程的MS患者来说是一种合理的治疗策略。综述目的：了解氧化应激在健康和疾病中的作用，探讨氧化应激对MS病理生理学的影响，并综述目前关于特定抗氧化疗法对MS患者（PwMS）疗效的证据，重点关注硫辛酸（LA）。最新发现：在动物和体内模型中进行的抗氧化干预研究显示，血清氧化应激标志物水平降低，抗氧化酶的水平和活性增加。对PwMS患者进行的抗氧化试验虽然通常样本量不足，但发现氧化应激标志物和抗氧化防御有短期改善，临床症状（疲劳、抑郁）也有较小程度的改善。迄今为止最有力的证据是一项针对继发进展型MS患者进行的为期2年的硫辛酸试验，该试验显示全脑萎缩显著减轻，步行速度有改善趋势。抗氧化疗法是一种有望在MS疾病的各个阶段和病程中发挥治疗作用的方法。需要进行严格且样本量充足的试验来确定其治疗益处。
