Ferrari R, Agnoletti L, Comini L, Gaia G, Bachetti T, Cargnoni A, Ceconi C, Curello S, Visioli O
University of Brescia, Chair of Cardiology, Spedali Civili, Italy.
Eur Heart J. 1998 Feb;19 Suppl B:B2-11.
Oxidative stress is a condition in which oxidant metabolites exert toxic effects because of their increased production or an altered cellular mechanism of protection. The heart needs oxygen but it is also susceptible to oxidative stress, which occurs during post-ischaemic reperfusion, for example. Ischaemia causes alterations in the defence mechanisms against oxygen free radicals. At the same time, production of oxygen free radicals increases. In man, there is evidence of oxidative stress during surgical reperfusion of the whole heart, or after thrombolysis, and it is related to transient left ventricular dysfunction or stunning. At present, there are few data on oxidative stress in the failing heart. It is not clear whether the defence mechanisms of the myocyte are altered or whether the production of oxygen free radicals is increased, or both. Recent data have shown a close link between oxidative stress and apoptosis. Importantly, tumour necrosis factor causes a rapid rise in intracellular reactive oxygen intermediates and apoptosis. This series of events is not confined to the myocytes, but also occurs at the level of endothelium, where tumour necrosis factor causes expression of inducible nitric oxide synthase, production of the reactive radical nitric oxide, oxidative stress and apoptosis. The immunological response to heart failure may result in endothelial and myocyte dysfunction through oxidative stress-mediated apoptosis. A better understanding of these mechanisms may lead to novel therapeutic strategies.
氧化应激是一种由于氧化代谢产物产生增加或细胞保护机制改变而产生毒性作用的状态。心脏需要氧气，但也易受氧化应激影响，例如在缺血后再灌注期间就会发生氧化应激。缺血会导致针对氧自由基的防御机制发生改变。与此同时，氧自由基的产生增加。在人类中，有证据表明在全心脏手术再灌注期间或溶栓后存在氧化应激，并且它与短暂性左心室功能障碍或心肌顿抑有关。目前，关于衰竭心脏中氧化应激的数据很少。尚不清楚心肌细胞的防御机制是否改变，或者氧自由基的产生是否增加，还是两者都有。最近的数据表明氧化应激与细胞凋亡之间存在密切联系。重要的是，肿瘤坏死因子会导致细胞内活性氧中间体迅速增加并引发细胞凋亡。这一系列事件不仅限于心肌细胞，也发生在内皮细胞水平，在那里肿瘤坏死因子会导致诱导型一氧化氮合酶表达、活性自由基一氧化氮产生、氧化应激和细胞凋亡。对心力衰竭的免疫反应可能通过氧化应激介导的细胞凋亡导致内皮细胞和心肌细胞功能障碍。更好地理解这些机制可能会带来新的治疗策略。
