Liew Reginald, Stagg Mark A, Chan Joachim, Collins Peter, MacLeod Kenneth T
Cardiac Medicine, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, United Kingdom.
Cardiovasc Res. 2004 Jan 1;61(1):66-76. doi: 10.1016/j.cardiores.2003.10.006.
The soy-isoflavone, genistein, appears to be cardioprotective partly through direct actions on the heart, although the relative benefits between men and women are not fully known. The purpose of the present study was to determine whether gender influences the acute electrophysiological actions of genistein at the level of isolated cardiac myocytes and to elucidate the mechanisms involved.
Left ventricular myocytes, isolated from weight-matched male and female guinea-pigs and rats, were field stimulated at a rate of 1 Hz in a superfusion chamber (37 degrees C). The effects of acute application of genistein on cell shortening and the Ca(2+) transients were measured. Electrophysiological recordings were performed using single electrode voltage-clamp.
Genistein increased cell contraction and the Ca(2+) transients in a concentration-dependent manner in myocytes from male guinea-pigs [by 54+/-11% and 22+/-4%, respectively (mean+/-S.E.M., p<0.001, n=18) at 40 microM], while having no significant corresponding effect in those from females. In contrast, genistein increased both parameters in myocytes obtained from male and female rats. The changes in guinea-pigs occurred despite inhibition of the L-type Ca(2+) current in both sexes (n>23, p<0.001). In order to explain these observations, we measured sarcoplasmic reticulum (SR) Ca(2+) contents by integrating the Na(+)/Ca(2+) exchanger currents (I(NCX)) following rapid caffeine application. Genistein increased I(NCX) integrals by 27% in males (n=12, p<0.01) and 20% in females (n=14, p<0.01). The increased SR Ca(2+) load in males, but not females, could be related to an impaired ability of the Na(+)/Ca(2+) exchanger to extrude Ca(2+).
We have demonstrated novel, gender-related differences in the acute cardiac actions of genistein, which can be attributed to actions at distinct points of the intracellular Ca(2+) cycle. Our results suggest that genistein may afford greater cardioprotection in females than in males.
大豆异黄酮染料木黄酮似乎部分通过对心脏的直接作用而具有心脏保护作用，尽管男女之间的相对益处尚不完全清楚。本研究的目的是确定性别是否会影响染料木黄酮在离体心肌细胞水平上的急性电生理作用，并阐明其中涉及的机制。
从体重匹配的雄性和雌性豚鼠及大鼠中分离出左心室肌细胞，在37℃的灌流室中以1Hz的频率进行场刺激。测量急性应用染料木黄酮对细胞缩短和Ca(2+)瞬变的影响。使用单电极电压钳进行电生理记录。
染料木黄酮以浓度依赖性方式增加雄性豚鼠心肌细胞的收缩和Ca(2+)瞬变[在40μM时分别增加54±11%和22±4%（平均值±标准误，p<0.001，n = 18）]，而对雌性心肌细胞没有显著的相应作用。相比之下，染料木黄酮增加了从雄性和雌性大鼠获得的心肌细胞中的这两个参数。尽管两性的L型Ca(2+)电流均受到抑制（n>23，p<0.001），但豚鼠中的变化仍然发生。为了解释这些观察结果，我们在快速应用咖啡因后通过整合Na(+)/Ca(2+)交换电流（I(NCX)）来测量肌浆网（SR）Ca(2+)含量。染料木黄酮使雄性的I(NCX)积分增加27%（n = 12，p<0.01），使雌性的I(NCX)积分增加20%（n = 14，p<0.01）。雄性而非雌性中SR Ca(2+)负荷的增加可能与Na(+)/Ca(2+)交换体排出Ca(2+)的能力受损有关。
我们已经证明了染料木黄酮急性心脏作用中与性别相关的新差异，这可归因于细胞内Ca(2+)循环不同点的作用。我们的结果表明，染料木黄酮对雌性的心脏保护作用可能比雄性更大。
