枳壳醇提物对大鼠离体胸主动脉环的收缩作用与机制  

Constrictive effects of ethanolic extract of Fructus Aurantii on rat thoracic aorta and the underlying mechanisms

作　　者：庄须国[1] 潘振伟[1] 刘晓丹[1] 李国玉[1] 牛慧莉[1] 吕延杰[1] 杨宝峰[1] 

机构地区：[1]哈尔滨医科大学药学院药理学教研室、省部共建生物医药国家重点实验室,黑龙江哈尔滨150081

出　　处：《中国药理学通报》2008年第6期810-814,共5页Chinese Pharmacological Bulletin

基　　金：黑龙江省科技厅攻关资助项目(NoGC06C33302);高等学院博士学科专项科研基金资助课题(No20040226014)

摘　　要：目的探讨枳壳醇提物(FAE)对大鼠离体胸主动脉的收缩作用与机制。方法制备Wistar大鼠胸主动脉环,采用离体血管实验方法,经生物信号采集与分析系统测定血管环张力的变化。结果FAE能够浓度依赖性的提高主动脉环张力,对去除内皮血管环的最大收缩幅度为(74±4.9)%,明显强于对内皮完整血管环的作用(44±3.4)%(P<0.01)。预孵一氧化氮合酶抑制剂L-NAME(300mmol.L-1)后,FAE对内皮完整的血管环的最大收缩幅度明显提高,达到(77±5.3)%(P<0.01)。在去除内皮的血管环上,维拉帕米(10-5mol.L-1,VER)及无钙液孵育均可明显阻断FAE的收缩作用,其最大收缩幅度分别降低(52±3.8)%和(49±3.7)%(P<0.01);激光扫描共聚焦检测细胞内钙的结果表明,FAE浓度依赖性(0.16、0.32g.L-1)的增加静息状态平滑肌细胞胞质内钙浓度。结论FAE能够浓度依赖性收缩大鼠胸主动脉,其作用机制可能与激活血管平滑肌上的电压依赖性钙通道,促使胞外Ca2+内流有关;同时,FAE也作用于血管内皮细胞,促进一氧化氮的释放,部分抵消其缩血管作用。Aim To explore the constrictive effect of Fructus Aurantii extract （FAE） on rat thoracic aorta and the underlying mechanisms. Methods Isometric tension measurements were used to study the effect of Fructus Aurantii on isolated rat thoracic aorta rings. Laser scanning confocal microscope was employed to measure the concentration of intracellular free calcium. Results FAE caused a dose-dependent contraction of the rat isolated aorta rings with or without endothelium, and the constrictive effect of FAE was more stronger on endothelium-denuded aorta rings （ 74 ± 4. 9 ） % than on endothelium-intact aorta rings （44 ± 3.4 ）% （P 〈 0. 01 ）. FAE induced contraction on the endotheliumintact rat aorta tings was increased by pretreatment with L-NAME （anitric oxide synthase inhibitor, 300 μm · L^-1）, from （44±3.4）% to （77±5.3）%（P〈 0. 01）. However, the constrictive effect of FAE was inhibited by pretreatment with Ca^2＋ -free K-H solution or verapamil （an L-type calcium channel antagonist, 10-s mol ~ L-t）, and the constrictive amplitude reduced by （52 ±. 8）% and （49±3.7）% respective ly （P 〈 0. 01 ）. FAE also dose-dependently increased the intracellular free calcium concentration. Conclusions FAE exerted a dose-dependent vasoconstrictive effects on rat isolated aorta rings by opening the L-type voltage-dependent Ca^2＋ channels, and enhancing the extracellular Ca^2＋ influx. FAE might also stimulate the release of nitric oxide from endothelium cells, which -partly compromised its vasoconstrictive effects.

关 键 词：枳壳醇提物 血管收缩 钙通道 一氧化氮 胸主动脉环 激光扫描共聚焦 

分 类 号：R-965.2[医药卫生] R331