槲皮素降低大鼠心率和心肌钙振荡频率和抑制小鼠心肌肥厚(英文)  

Quercetin decreased heart rate and cardiomyocyte Ca^(2+) oscillation freauencv in rats and prevented cardiac hypertrophy in mice

作　　者：王瑜[1] 汪红仪[1] 袁肇侃 赵晓宁[1] 王金晞[2] 张祖暄[1] 

机构地区：[1]南京大学医学院 [2]南京大学配位化学国家重点实验室

出　　处：《中国药理学报》1999年第5期426-430,共5页Acta Pharmacologica Sinica

基　　金：Project supported by the Natural Science Foundation of Jiangsu Province, № BK93030311

摘　　要：目的:研究槲皮素对心肌兴奋收缩耦联及构型重建的影响。方法:经动脉插管记录大鼠血流动力学;缩窄小鼠腹主动脉致心肌肥厚;检测Fura 2-AM负载的培养大鼠心肌细胞内游离钙([Ca^(2+)]_i)及钙振荡,结果:槲皮素剂量相关地降低大鼠窦性心率,而动脉血压、左室压及其微分改变轻微;10-250 μmol·L^(-1)时浓度依赖性降低培养心肌自发钙振荡频率,100μmol·L^(-1)时预防异丙肾上腺素及哇巴因加速钙振荡频率,但不抑制静息[Ca^(2+)]_i.和自发钙振荡及二药增高的振荡幅度,槲皮素还抑制血管紧张素Ⅱ而非高钾的升[Ca^(2+)]_i作用,槲皮素120 mg·kg^(-1)·d^(-1)5 d灌胃不改变假手术鼠的心室与体重之比,但显著抑制腹主动脉结扎小鼠的心室肥大,结论:槲皮素降低心肌钙振荡频率和心肌肥厚但不直接影响心脏兴奋收缩耦联。AIM: To study the effects of quercetin (Que) on myocardial excitation-contraction coupling and cardiac remodeling. METHODS: Left ventricles and femoral arteries of rats were cannulated for hemodynamic recording. Mouse cardiac hypertrophy was induced by abdominal aortic coarctation ( AAC ). Cultured myocardial cells in neonatal rats were loaded with Fura 2-AM. The intracellular calcium ([ Ca2 + ]i) and spontaneous [Ca2+ ]i oscillations ([Ca2+ ]i-SO) were tested by AR-CM-MIC cation measurement system. RESULTS: Que 3 or 25 mg·kg-1 iv in rats decreased heart rate from (420±19) to (390± 15) and (314±18) beat·min-1, respectively, companied with very modest changes in both left ventricular pressures (LVP) and its differential dpLV/dtmax. Que 10, 50, 250 μmol· L-1 concentration-dependently slowed the frequency of [Ca2+ ]i-SO in cultured myocardial cells from (26 ±4) to (25±3), (18±4), and (12±3) time· min-1, respectively, but did not change their resting [ Ca2+ ]i or amplitudes of [ Ca2+ ]i-SO. Similarly, the increases in frequency of [Ca2+ ]i-SO caused by either isoproterenol (Iso) or ouabain (Oua) were prevented by Que 100 μmol· L-1, while the simultaneous increases in amplitude of [Ca2 + ]i-SO remained. Besides, [ Ca2 + ]i rises excited byangiotensin Ⅱ (Ang Ⅱ ) but not high [ K+ ]o were prevented by Que 100μmol·L-1. Daily administration of Que 120 mg·kg-1 ig for 5 d markedly prevented the cardiac hypertrophy in AAC mice, without effects on the ventricular mass to body weight ratio (VM/BW) in sham-operated mice. CONCLUSION: Que decreased myocardial [Ca2+ ] i-oscillation frequency and prevented cardiac remodeling, but had no direct effect on cardiac excitation-contraction coupling.

关 键 词：槲皮素 心动过缓 心肌 左心室肥大 药理 

分 类 号：R972[医药卫生—药品] R965.2[医药卫生—药学]