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缺血再灌注损伤中心肌抗氧化剂的状态

Status of myocardial antioxidants in ischemia-reperfusion injury.

作者信息

Dhalla N S, Elmoselhi A B, Hata T, Makino N

机构信息

Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, 351 Tache Ave., Manitoba, R2H 2A6, Winnipeg, Canada.

出版信息

Cardiovasc Res. 2000 Aug 18;47(3):446-56. doi: 10.1016/s0008-6363(00)00078-x.

Abstract

BACKGROUND

Myocardial ischemia-reperfusion represents a clinically relevant problem associated with thrombolysis, angioplasty and coronary bypass surgery. Injury of myocardium due to ischemia-reperfusion includes cardiac contractile dysfunction, arrhythmias as well as irreversible myocyte damage. These changes are considered to be the consequence of imbalance between the formation of oxidants and the availability of endogenous antioxidants in the heart.

OBSERVATIONS

An increase in the formation of reactive oxygen species during ischemia-reperfusion and the adverse effects of oxyradicals on myocardium have now been well established by both direct and indirect measurements. Although several experimental studies as well as clinical trials have demonstrated the cardioprotective effects of antioxidants, some studies have failed to substantiate the results. Nonetheless, it is becoming evident that some of the endogenous antioxidants such as glutathione peroxidase, superoxide dismutase, and catalase act as a primary defense mechanism whereas the others including vitamin E may play a secondary role for attenuating the ischemia-reperfusion injury. The importance of various endogenous antioxidants in suppressing oxidative stress is evident from the depression in their activities and the inhibition of cardiac alterations which they produce during ischemia-reperfusion injury. The effects of an antioxidant thiol containing compound, N-acetylcysteine, and ischemic preconditioning were shown to be similar in preventing changes in the ischemic-reperfused hearts.

CONCLUSIONS

The available evidence support the role of oxidative stress in ischemia-reperfusion injury and emphasize the importance of antioxidant mechanisms in cardioprotection.

摘要

背景

心肌缺血再灌注是一个与溶栓、血管成形术和冠状动脉搭桥手术相关的临床重要问题。缺血再灌注导致的心肌损伤包括心脏收缩功能障碍、心律失常以及不可逆的心肌细胞损伤。这些变化被认为是心脏中氧化剂生成与内源性抗氧化剂可用性失衡的结果。

观察结果

通过直接和间接测量,现已充分证实缺血再灌注期间活性氧生成增加以及氧自由基对心肌的不利影响。尽管多项实验研究以及临床试验已证明抗氧化剂具有心脏保护作用,但一些研究未能证实这些结果。然而,越来越明显的是,一些内源性抗氧化剂,如谷胱甘肽过氧化物酶、超氧化物歧化酶和过氧化氢酶,起着主要防御机制的作用,而其他包括维生素E在内的抗氧化剂可能在减轻缺血再灌注损伤方面起次要作用。各种内源性抗氧化剂在抑制氧化应激中的重要性,从它们在缺血再灌注损伤期间活性的降低以及对心脏改变的抑制中可见一斑。一种含抗氧化剂硫醇的化合物N - 乙酰半胱氨酸的作用与缺血预处理在预防缺血再灌注心脏变化方面相似。

结论

现有证据支持氧化应激在缺血再灌注损伤中的作用,并强调抗氧化机制在心脏保护中的重要性。

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