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白藜芦醇降低大鼠心室肌细胞内游离钙浓度

刘政, 张利萍, 马会杰, 王川, 李明, 王庆山

河北医科大学基础医学研究所生理室.河北,石家庄 050017；河北医科大学基础医学研究所药理室.河北,石家庄 050017

摘要

实验旨在研究白藜芦醇(resveratrol)对大鼠心室肌细胞内钙浓度(intracellular calcium concentratoin, [Ca~(2+)]_(i))的影响。应用激光共聚焦显微镜技术记录心室肌细胞内的钙荧光强度。结果表明：在正常台氏液和无钙台氏液中，白藜芦醇(15---60 #mu#mol/L)呈浓度依赖性地降低[Ca~(2+)]_(i)。蛋白酪氨酸磷酸酶抑制剂正钒酸钠(sodium orthovanadate, 1.0 mmol/L)和L型Ca~(2+)通道激动剂Bay K8644 (10 #mu#mol/L)可部分抑制正常台氏液中白藜芦醇的效应。但NO合酶阻断剂 L-NAME (1.0 mmol/L)对白藜芦醇的作用无影响。白藜芦醇也能明显抑制无钙台氏液中由低浓度ryanodine (1.0 nmol/L)引起的[Ca~(2+)]_(i)增加。当细胞外液钙浓度由1 mmol/L增加到10 mmol/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，白藜芦醇(60 #mu#mol/L)可降低钙波的传播速度和持续时间，最终阻断钙波。结果提示，白藜芦醇能够降低心室肌细胞内游离钙浓度，此作用可能与其抑制电压依赖性Ca~(2+)通道、酪氨酸激酶和肌浆网内钙释放有关。

关键词： 白藜芦醇; 大鼠; 心室肌细胞; 细胞内钙; 钙通道

Resveratrol reduces intracellular free calcium concentration in rat ventricular myocytes

Liu Zheng, Zhang Liping, Ma Huijie, Wang Chuan, Li Ming, Wang Qingshan

Department of Physiology, Institute of Basic Medical Sciences, Hebei Medical University.Shijiazhuang 050017,Hebei；China

Abstract

Resveratrol (trans-3,4’,5-trihydroxy stilbene), a phytoalexin found in grape skins and red wine, has been reported to have a wide range of biological and pharmacological properties. It has been speculated that resveratrol may have cardioprotective activity. The objective of our study was to investigate the effects of resveratrol on intracellular calcium concentratoin ([Ca~(2+)]_(i)) in rat ventricular myocytes. [Ca~(2+)]_(i) was detected by laser scanning confocal microscopy. The results showed that resveratrol (15--60 #mu#mol/L) reduced [Ca~(2+)]_(i) in normal and Ca~(2+)-free Tyrode's solution in a concentration-dependent manner. The effects of resveratrol on [Ca~(2+)]_(i) in normal Tyrode's solution was partially inhibited by pretreatment with sodium orthovanadate (Na_(3)VO_(4), 1.0 mmol/L, P<0.01), an inhibitor of protein tyrosine phosphatase, or L-type Ca~(2+) channel agonist Bay K8644 (10 #mu#mol/L, P<0.05), but could not be antagonized by NO synthase inhibitor L-NAME (1.0 mmol/L). Resveratrol also markedly inhibited the ryanodine-induced [Ca~(2+)]_(i) increase in Ca~(2+)-free Tyrode's solution (P<0.01). When Ca~(2+) waves were produced by increasing extracellular Ca~(2+) concentration from 1 to 10 mmol/L, resveratrol (60 #mu#mol/L) could reduce the velocity and duration of propagating waves, and block the propagating waves of elevated [Ca~(2+)]_(i). These results suggest that resveratrol may reduce the [Ca~(2+)]_(i) in isolated rat ventricular myocytes. The inhibition of voltage-dependent Ca~(2+) channel and tyrosine kinase, and alleviation of Ca~(2+) release from sarcoplasmic reticulum (SR) are possibly involved in the effects of resveratrol on rat ventricular myocytes. These findings could help explain the protective activity of resveratrol against cardiovascular disease.

Key words: resveratrol;Rat;Myocytes;Intracellular calcium;Ca~(2+) channel

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引用本文：

刘政, 张利萍, 马会杰, 王川, 李明, 王庆山. 白藜芦醇降低大鼠心室肌细胞内游离钙浓度 [J]. 生理学报 2005; 57 (5): .

Liu Zheng, Zhang Liping, Ma Huijie, Wang Chuan, Li Ming, Wang Qingshan. Resveratrol reduces intracellular free calcium concentration in rat ventricular myocytes . Acta Physiol Sin 2005; 57 (5): (in Chinese with English abstract).