氧化苦参碱的血管舒张作用及其机制研究  

Vasodilatory Effect of Oxymatrine and Its Mechanisms

作　　者：李亚娟[1] 唐宁[1] 卞卡[1,2] 

机构地区：[1]上海中医药大学穆拉德中药现代化研究中心,上海201203 [2]美国德克萨斯大学休斯顿医学院综合生物及药理学系,德克萨斯大学分子医学研究所,休斯顿tx77030

出　　处：《上海中医药杂志》2009年第4期62-66,共5页Shanghai Journal of Traditional Chinese Medicine

基　　金：国家教育部重点科研基金资助项目(05ZZ11);上海市教委基金资助项目(05Jg05053);上海市科委基础研究重点项目(05JC14056);国家科技支撑计划基金资助项目(2006BAI11B08-03)

摘　　要：目的观察氧化苦参碱(Oxymatrine)的血管舒张作用及其机制。方法采用大鼠离体血管功能实验装置,描记张力变化,每组血管来自6只同批大鼠,分别保留或去除内皮,各阻断剂预处理25min之后做Oxymatrine舒张曲线;Oxymatrine预处理10min之后做钙离子收缩曲线。结果Oxymatrine(0.9mmol/L～34.2mmol/L)剂量依赖性地舒张苯肾上腺素(PE)预收缩的内皮完整或去除内皮的大鼠胸主动脉环,内皮去除前后最大舒张效应Emax分别为(95.00±1.22)%和(95.90±1.17)%,而EC50由完整内皮的9.98mmol/L到12.79mmol/L(P<0.05);亚硝基左旋精氨酸甲酯(L-NAME)0.1mmol/L、鸟苷酸环化酶抑制剂(ODQ)0.01mmol/L预处理可抑制Oxymatrine对内皮完好血管的舒张效应(P<0.05);Oxymatrine(4.37mmol/L、8.63mmol/L)不能抑制无钙高钾液中Ca2+收缩曲线。钾通道阻断剂四乙胺(TEA)3mmol/L、氯化钡(BaCl2)0.1mmol/L预处理可显著减弱Oxymatrine对内皮完好血管的舒张效应,药物处理前后最大舒张效应Emax分别为:对照组(96.00±1.02)%、TEA组(53.90±1.22)%、BaCl2组(39.90±2.01)%,EC50分别为:对照组12.79mmol/L、TEA组32.74mmol/L和BaCl2组36.22mmol/L(P<0.01)。结论Oxymatrine具有舒张血管作用,其机制与内皮NO-cGMP途径和血管平滑肌大电导钙激活钾通道和内向整流钾通道有关。Objective To investigate the vasodilatory effect of oxymatrine and its mechanisms. Methods This study was performed with the isolated rats＇ aortic rings in organ bath, and the tension changes of aortic rings were recorded. The rings of each group were taken from 6 rats, and with endothetium intact and removed respectively; some groups were pretreated with different inhibitors for 25min, and then make the Oxymatrine relaxation curve; other groups with oxymatrine pretreated for 10 min and then make the Ca^2 ＋ contraction curves. Results Oxymatrine（0.9 -34.2 mmol/L） concentration-dependently relaxed isolated aorta ring, and the maximum relaxation by oxymatrine was 95% ±1.22% in endothelimn intact rings and 95.9%±1.17% in endothelium removed rings while the 1 μmol/L forskolin-induced vasodilation was taken as 100%. EC50 for oxymatrine-induced vasodilation was 9.98 mmol/L in endothelium intact group and 12.79 mmol/L in endothelium removed groups. The vasodilatory effect by oxymatrine was significantly inhibited by 0.1 mmol/L L-NAME （ P 〈0.05 ） and 0. 01 mmol/L ODQ（ P 〈0.05 ） in the preparations with endothelium. The oxymatrine（4.37 mmol/L, 8.63 mmol/L） incubation could not attenuate potassium-stimulated Ca^2 ＋ -dependent contraction due to Ca^2 ＋ influx. The vasodilatory effect of oxymatrine was significantly inhibited by potassium channel blocker TEA 3 retool/Land BaC12 0. lmmoL/L, the Emax was 96.0% ±1.02% in control group,53.9%±1.22% in TEA group and 39.9%±2.01% in BaCl2 group（P 〈0.01 ）. Conclusion Oxymatrine may serve as a potassium channel opener which has effects on both BKCa and Kir on VSMC, and the compound also partly dilates blood vessel through NO-cGMP signal pathway.

关 键 词：氧化苦参碱 血管内皮细胞 一氧化氮-环鸟甘酸 血管平滑肌细胞 钾通道 

分 类 号：R285.5[医药卫生—中药学]