心肌缺血应激：心肌细胞 Ca²⁺、性别和性激素。

Cardiac ischaemic stress: cardiomyocyte Ca²⁺, sex and sex steroids.

Cardiac Phenomics, Department of Physiology, University of Melbourne, Melbourne, Victoria, Australia.

Clin Exp Pharmacol Physiol. 2011 Oct;38(10):717-23. doi: 10.1111/j.1440-1681.2011.05567.x.

Abstract

Important sex differences exist in ischaemic heart disease. Oestrogen has been conventionally regarded as providing a cardioprotective benefit and testosterone frequently perceived to exert a deleterious effect. However, there is accumulating evidence that argues against this simple dichotomy, suggesting that the influence of oestrogen and testosterone conferring benefit or detriment may be context specific. 2. Cardiomyocyte calcium (Ca(2+)) loading is recognized to be a major factor in acute ischaemia-reperfusion pathology, promoting cell death, contractile dysfunction and arrhythmogenic activity. Ca(2+)/calmodulin-dependent kinase II (CaMKII) is a mediator of many of the cardiomyocyte Ca(2+)-related pathologies in ischaemia-reperfusion. Cardiomyocyte Ca(2+)-handling processes have been shown to be modulated by the actions of oestrogen and testosterone. A role for these sex steroids in influencing CaMKII activation is argued. 3. Although many experimental studies of oestrogen manipulation can identify a cardioprotective role for this sex steroid, there are also numerous reports that fail to demonstrate sex differences in postischaemic recovery. Experimental studies report that testosterone can be protective in ischaemia-reperfusion in males and females in some settings. 4. Further studies of sex steroid influence in the ischaemic heart will allow the development of therapeutic interventions that are specifically targeted for male and female hearts.

摘要

缺血性心脏病存在重要的性别差异。雌激素通常被认为具有心脏保护作用，而睾丸酮则被认为具有有害作用。然而，越来越多的证据表明，这种简单的二分法并不正确，表明雌激素和睾丸酮的影响可能是特定于具体情况的。
心肌细胞钙离子（Ca(2+))负荷被认为是急性缺血再灌注病理的一个主要因素，它会促进细胞死亡、收缩功能障碍和心律失常活性。钙调蛋白依赖性激酶 II（CaMKII）是缺血再灌注过程中许多与心肌细胞 Ca(2+)相关的病理的介导者。已经证明，心肌细胞 Ca(2+)处理过程受雌激素和睾丸酮的作用调节。有人认为这些性激素在影响 CaMKII 激活方面发挥作用。
尽管许多关于雌激素操作的实验研究可以确定这种性激素具有心脏保护作用，但也有许多报告未能证明缺血后恢复存在性别差异。实验研究报告称，在某些情况下，睾丸酮在男性和女性的缺血再灌注中具有保护作用。
进一步研究性激素对缺血性心脏的影响将有助于开发针对男性和女性心脏的特定治疗干预措施。