三羟异黄酮对豚鼠心室肌细胞内游离钙浓度的影响

用激光共聚焦显微镜观察研究三羟异黄酮(genistein,GST)对豚鼠心室肌细胞内游离钙浓度(Ca^2 ]i)的影响。结果用相对荧光强度(FI-F0／FX0,％)表示。实验结果显示,在正常台氏液、无钙台氏液和正常台氏液中加入3mmol／L EGTA后,GST(10～40μmol／L)浓度依赖性地降低细胞内钙浓度。蛋白酪氨酸磷酸酶抑制剂正钒酸钠(sodium orthovanadate)和L-型Ca^2 通道激动剂Bay K8644可部分抑制正常台氏液时GST的效应。当细胞外液钙浓度由1mmol／L增加到10mmol／L而诱发心室肌细胞钙超载时,部分心室肌细胞产生可传播的钙波,GST(40μmol／L)可降低钙波的传播速度和持续时间,最终阻断钙波。以上结果提示,GST降低心室肌细胞内游离钙浓度,此作用与其抑制电压依赖性Ca^2 通道、减弱酪氨酸激酶抑制和豚鼠心室肌细胞肌浆网内钙释放有关。

Effects of genistein on intracellular free-calcium concentration in guinea pig ventricular myocytes

The effects of genistein (GST) on intracellular calcium concentration (Ca2+]i) were investigated in guinea pig ventricular myocytes. Ca2+]i was detected by confocal microscopy and represented by relative fluorescent intensity (FI-F0) /FI0, %). The results showed that GST (10-40 umol/L) reduced Ca2+]i in normal Tyrode's solution, Ca2+-free Tyrode's solution and normal Tyrode's solution containing 3 mmol/L EGTA in a concentration-dependent manner. The effects of GST on Ca2+]i in normal Tyrode's solution were partially inhibited by pretreatment with sodium orthovanadate, a potent inhibitor of protein tyrosine phosphatase, or L-type Ca2+ channel agonist Bay K8644. GST also markedly inhibited the ryanodine-induced Ca2+]i responses in Ca2*-free Tyrode's solution. When Ca2+ waves were produced by increasing extracellular Ca2+ concentration from 1 to 10 mmol/L, GST (40 umol/L) could block the propagating waves of elevated Ca2+]i' and reduce the velocity and duration of propagating waves. These results suggest that GST may reduce the Ca2+]i in isolated guinea pig ventricular myocytes. The inhibition of voltage-dependent Ca2+ channel, tyrosine kinase inhibition, and alleviation of Ca2+ release from SR are possibly involved in the GST effect.