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抗氧化疗法作为治疗系统性硬化症的一种新方法的新兴潜力。

Emerging potentials for an antioxidant therapy as a new approach to the treatment of systemic sclerosis.

作者信息

Simonini G, Pignone A, Generini S, Falcini F, Cerinic M M

机构信息

Department of Pediatrics, University of Florence, Institute of Internal Medicine, Italy.

出版信息

Toxicology. 2000 Nov 30;155(1-3):1-15. doi: 10.1016/s0300-483x(00)00272-9.

Abstract

Oxidative stress, favoring disease progression by a rapid degeneration of endothelial cell function is deeply involved in Systemic Sclerosis (SSc) pathogenesis. Raynaud's phenomenon (RP), present in 90% of patients with SSc, provoking frequent daily episodes of hypoxia-reperfusion injury, produces several episodes of free radicals-mediated endothelial derangement. These events results in a positive feedback effect of luminal narrowing and ischemia and therefore to the birth of a vicious cycle of oxygen free radicals (OFR) generation, leading to endothelial damage, intimal thickening and fibrosis. Thus ischemia and reperfusion are two criticals events that may induce oxidative stress and inactivation of antioxidant enzymes. In RP and SSc, a reduced concentration of ascorbic acid, alpha-tocopherol and beta-carotene as well as low values of Selenium have been reported. This antioxidative potential deficiency increases the propensity to oxidative stress. favoring the development of injury mediated by OFR. We reviewed several antioxidant compounds, aiming at their capacity of reverting endothelial dysfunction and damage, scavenging lipid peroxidation and reducing multiple episodes of hypoxia-reperfusion injury. In order to interrupt SSc vicious cycle, we propose a main strategy for SSc treatment by a supplementation of antioxidants and different kind of drugs with antioxidant property, such as Lazaroids, Resveratrol, Melatonin and Probucol.

摘要

氧化应激通过内皮细胞功能的快速退化促进疾病进展,在系统性硬化症(SSc)发病机制中起重要作用。雷诺现象(RP)存在于90%的SSc患者中,每天频繁引发缺氧-再灌注损伤,产生多次自由基介导的内皮紊乱。这些事件导致管腔狭窄和缺血的正反馈效应,从而引发氧自由基(OFR)生成的恶性循环,导致内皮损伤、内膜增厚和纤维化。因此,缺血和再灌注是可能诱导氧化应激和抗氧化酶失活的两个关键事件。在RP和SSc中,已报道抗坏血酸、α-生育酚和β-胡萝卜素浓度降低以及硒值较低。这种抗氧化潜能缺乏增加了氧化应激倾向,有利于OFR介导的损伤发展。我们综述了几种抗氧化化合物,旨在研究它们恢复内皮功能障碍和损伤、清除脂质过氧化以及减少多次缺氧-再灌注损伤的能力。为了打断SSc恶性循环,我们提出了一种通过补充抗氧化剂和具有抗氧化特性的不同种类药物(如拉扎罗类药物、白藜芦醇、褪黑素和普罗布考)来治疗SSc的主要策略。

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