玄参提取物舒张血管作用及机制研究

目的观察玄参提取物(extract from scrophulariae,radix,ES)血管舒张作用及其机制。方法采用大鼠离体血管环功能实验装置,记录张力变化,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25 min后做ES舒张曲线;ES预处理10 min后做钙离子收缩曲线。结果玄参提取物(ES)(0.05 mg/L~2 000 mg/L)剂量依赖性地舒张苯肾上腺素(PE)预收缩的内皮完好或内皮去除大鼠胸主动脉环,在去除内皮前后最大舒张效应(E max)无显著性差异,分别为(78.29%±1.20%)和(76.89%±3.20%);亚硝基左旋精氨酸甲酯(L-NAME)、吲哚美辛、普萘洛尔、鸟甘酸环化酶抑制剂(ODQ)预处理不能抑制ES的血管舒张效应;ES(500 mg/L)对血管紧张素Ⅱ、前列环素F2α、多巴胺、血管加压素收缩血管显示出抑制效应(P0.05),而对5-羟色胺、内皮素-1(ET-1)的收缩作用无影响;ES(1 000 mg/L)预处理可显著抑制无钙高钾液中由Ca2+内流引起的血管收缩(P0.05),ES(500 mg/L)预处理可抑制无钙液中PE血管收缩强度(P0.01);钾通道阻断剂四乙胺(TEA)3 mmol/L、BaCl20.1 mmol/L预处理可阻断ES血管舒张作用(P0.01),半数效应浓度EC50分别为TEA组(1 900 mg/L)、BaCl2组(1 400 mg/L)。结论 ES具有非内皮依赖性血管舒张作用,其机制与影响血管平滑肌上钾通道有关;部分与阻断钙通道,调节细胞内钙离子浓度相关。

Vasodilation activity of extract from scrophulariae and its mechanism

Objective To investigate the vasodilation activity of extract from scrophulariae and its mechanism. Methods This study was performed with the isolated rat aortic rings in vitro, and the tension changes of aortic rings were recorded. The endothelium was reserved and removed. The ES diastole curve after 25 rain was treated by blocker; then calcium ion shrinkage curve after 10 min was treated by ES. Results ES （0.05 mg/L - 2000 rag/L） concentration- dependently relaxed the aortic rings pre-constricted with PE, the maximum relaxation by ES was 78.29% ± 1.20% in endothelium intact group and 76. 89%± 3.20% in endothelium removed group rings while the 1 μmol/L forskolin induced vasodilation was taken as 100%. L-NAME, indomethacin, ODQ and propranolol pretreated can not inhibit the vasodilation by ES ; on the other hand, pre-treated of rings with ES 500 mg/L markedly blocked vasoconstriction induced by Ang H , PGF2a , dopamine and vasopressin （P 〈 0.05 ） , but not 5-HT and endothelin-1 ; the ES1 000 mg/L incubation significantly suppressed the contraction curve of CaC]： in Ca： ＋ free medium containing of KC1 （ P 〈 0.05 ）, in addition, ES 500 mg/L pretreated also inhibited contraction by PE in Ca2 ＋ free solution （P 〈0.01 ）. The vasorelaxant effect of ES was significantly inhibited by potassium channel blocker TEA 3mmol/L and BaCI2 0. lmmol/L, the EC50 was 1 900 mg/L and 1 400 mg/L respectively （P 〈0.01 ）. Conclusion Our study suggested that ES can endothelium-independently relax rat aortic rings in vitro. The mechanisms may be related with potassium channel opening on VSMC and also partly through calcium channels blocking.