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维生素E对心肌缺血再灌注损伤的治疗潜力。

Therapeutic potential of vitamin E against myocardial ischemic-reperfusion injury.

作者信息

Janero D R

机构信息

Research Department, CIBA-GEIGY Corporation, Summit, NJ 07901.

出版信息

Free Radic Biol Med. 1991;10(5):315-24. doi: 10.1016/0891-5849(91)90038-5.

Abstract

Myocardial ischemia is a disease process characterized by reduced coronary flow such that the supply of nutritive blood to heart muscle (myocardium) is insufficient for normal myocardial aerobic metabolism. Prompt reestablishment of coronary flow by invasive and noninvasive clinical procedures is the most direct and effective means of limiting myocardial damage in ischemic heart disease patients, although reperfusion carries with it an injury component which may reflect, at least to some degree, the toxic effects of partially reduced oxygen species and their participation in degenerative cellular processes such as membrane lipid peroxidation. Vitamin E, a lipophilic, chain-breaking antioxidant, is a prominent membrane constituent in heart muscle, where it modulates/regulates various aspects of heart muscle-cell metabolism and function. Vitamin E's beneficial effects against experimentally induced oxidative damage to the heart, along with inverse epidemiological correlations between plasma vitamin E level and either anginal pain or mortality due to ischemic heart disease, suggest that vitamin E might have protective and therapeutic roles against myocardial ischemic-reperfusion injury. Laboratory investigations aimed at addressing this possibility have demonstrated that vitamin E supplementation protects isolated hearts against ischemic-reperfusion injury, and relatively more inconsistent and limited data document cardioprotective effects of vitamin E in some animal models of myocardial ischemia-reperfusion, especially when administered prior to the ischemic period. Clinical attempts to establish whether vitamin E has therapeutic benefit in ischemic heart disease patients remain inconclusive, having relied upon a variety of nonuniformly controlled protocols and a single, rather subjective endpoint (anginal pain). Consequently, although laboratory data constitute a conceptual context for and indirect support of the idea that vitamin E could be a cardioprotectant against ischemic-reperfusion injury, compelling clinical evidence regarding vitamin E's therapeutic potential in the ischemic heart-disease patient is lacking. Elective coronary revascularization would appear to provide an attractive clinical setting for evaluating the therapeutic efficacy of vitamin E in the context of cardiac ischemia-reperfusion. Further biochemical work would still be required to define how vitamin E exerts any cardioprotective effect observed in these patients.

摘要

心肌缺血是一种疾病过程,其特征为冠状动脉血流减少,致使供应给心肌的营养性血液不足以维持正常的心肌有氧代谢。通过侵入性和非侵入性临床手段迅速重建冠状动脉血流,是限制缺血性心脏病患者心肌损伤的最直接、最有效的方法,尽管再灌注会带来损伤成分,这可能至少在一定程度上反映了部分还原氧物种的毒性作用及其参与诸如膜脂质过氧化等退行性细胞过程。维生素E是一种亲脂性、链断裂抗氧化剂,是心肌中的一种重要膜成分,在心肌细胞代谢和功能的各个方面发挥调节作用。维生素E对实验性诱导的心脏氧化损伤具有有益作用,以及血浆维生素E水平与心绞痛或缺血性心脏病死亡率之间的反向流行病学关联,表明维生素E可能对心肌缺血再灌注损伤具有保护和治疗作用。旨在探讨这种可能性的实验室研究表明,补充维生素E可保护离体心脏免受缺血再灌注损伤,并且相对更不一致且有限的数据证明了维生素E在一些心肌缺血再灌注动物模型中的心脏保护作用,尤其是在缺血期之前给予时。关于维生素E在缺血性心脏病患者中是否具有治疗益处的临床尝试仍无定论,这依赖于各种控制不统一的方案和单一、相当主观的终点(心绞痛)。因此,尽管实验室数据为维生素E可能是一种抗缺血再灌注损伤的心脏保护剂这一观点提供了概念背景和间接支持,但缺乏关于维生素E在缺血性心脏病患者中的治疗潜力的确凿临床证据。选择性冠状动脉血运重建似乎为评估维生素E在心脏缺血再灌注情况下的治疗效果提供了一个有吸引力的临床环境。仍需要进一步的生化研究来确定维生素E如何在这些患者中发挥任何观察到的心脏保护作用。

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