【摘要】 背景:二氢石蒜碱在外周能抑制交感神经末梢释放儿茶酚胺,阻断α,β肾上腺素能受体,具有扩血管、降血压,抗缺糖、缺氧作用。目的:应用重酒石酸去甲肾上腺素和KCl引起血管收缩反应,观察二氢石蒜碱对家兔脑基底动脉、胸主动脉及心室乳头肌的选择性作用。设计:观察性对比实验。单位:郧阳医学院药理教研室。材料:实验于2001-03/07在郧阳医学院药理教研室的科研室进行,选择46只成年健康新西兰白兔。方法:新西兰白兔在麻醉下耳缘静脉注射10mL空气处死,迅速取出脑、胸主动脉及心脏。将基底动脉、胸主动脉制成4.0～5.0mm的血管环,打开心脏分离心室乳头肌,分别连接张力换能器。实验观察:①记录重酒石酸去甲肾上腺素或KCl单用时收缩曲线的变化:胸主动脉给予重酒石酸去甲肾上腺素0.1mmol/L或KCl60mmol/L引起血管亚最大收缩,待收缩曲线平稳后,分别用累积法加入不同浓度的二氢石蒜碱或尼莫地平。基底动脉给予重酒石酸去甲肾上腺素0.1mmol/L或KCl60mmol/L,待血管收缩达峰值后,冲洗液每20min换1次,共3次。再用不同浓度二氢石蒜碱或尼莫地平,20min后再加入重酒石酸去甲肾上腺素或KCl,待曲线平稳后,观察每单剂药物所致收缩曲线的变化。②记录电刺激心室乳头肌时收缩的幅度变化:1次/s,波宽3ms,阈电压的120%强度电刺激以引发心室乳头肌同步收缩活动,待收缩曲线平稳后,分别用累加法加入二氢石蒜碱或尼莫地平。主要观察指标:①离体基底动脉、胸主动脉及心室乳头肌收缩张力变化。②二氢石蒜碱或尼莫地平对重酒石酸去甲肾上腺素或KCl所致家兔血管环收缩的半数有效浓度值。结果:46只家兔离体基底动脉、胸主动脉及心室乳头肌标本均进入实验分析。①二氢石蒜碱使基底动脉静息张力升高,尼莫地平则使其降低,对胸主动脉无影响。②重酒石酸去甲肾上腺素、KCl所致基底动脉及胸主动脉收缩,二氢石蒜碱使之呈剂量依赖性松弛,其半数有效浓度值:对基底动脉分别为(6.69±3.12)×10-4,(3.41±1.52)×10-3mmol/L;对胸主动脉分别为(1.49±0.59)×10-3,(2.91±0.99)×10-3mmol/L。拮抗重酒石酸去甲肾上腺素所致基底动脉收缩作用明显强于KCl。尼莫地平对KCl所致收缩的抑制显著强于对重酒石酸去甲肾上腺素。③重酒石酸去甲肾上腺素或尼莫地平对电刺激诱发心室乳头肌的收缩均有剂量依赖性抑制作用,二氢石蒜碱对电刺激诱发心室乳头肌收缩的半数有效浓度显著高于重酒石酸去甲肾上腺素所致基底动脉。结论:二氢石蒜碱对家兔基底动脉有明显的选择性作用,在基底动脉可能存在使该血管平滑肌收缩的α1受体亚型和使之舒张的β受体。二氢石蒜碱作用可能与对这些受体的阻断作用相关。其选择性作用可能有助于改善缺血区的血液供给。更多还原

【Abstract】 BACKGROUND: Dihydrolycorine (DL) can inhibit the peripheral release of catecholamine from sympathetic nerve ending and block α, β adrenalinergic receptor. It has multiple pharmacological actions, such as vascular dilation, hypotension, anti-hypoglycemia and anti-ischemia. OBJECTIVE: To investigate the selective effect of DL on basilar artery, thoracic aorta and ventricular papillary muscle of rabbit by means of observing the vasoconstriction induced by noradrenaline bitartrate and KCl. DESIGN: Observation of comparative experiment. SETTING: Pharmacological Department of Yunyang Medical College. MATERIALS: This study was carried out at Pharmacological Department of Yunyang Medical College between March and July 2001, and 46 adult healthy New Zealand rabbits were selected. METHODS: New Zealand rabbits were put to death by intravenous injection of 10 mL air from the vein of aural edge, and soon after death, brain,thoracic aorta and heart were obtained. Basilar artery and thoracic aorta was linked into 4.0-5.0 mm vascular rings; meanwhile, ventricular papillary muscle were separated and connected with tension transducer. Observations: ① Changes of vasoconstriction curve due to administration of single dose of noradrenaline bitartrate or KCl: Sub-maximal constriction of thoracic aorta was induced by 0.1 mmol/L noradrenaline bitartrate or W60 mmol/L KCl, and when constriction curve became stable, DL or nimodipine of different dosage was added. Basilar artery was exposed to 0.1 mmol/L noradrenaline bitartrate or 60 mol/L KCl, and rinsing fluid was changed once every 20 minutes and thrice in all when vasocontratcion reached the peak level, then different dosage of DL or nimodipine was added 20 minutes later, and the changes of vasoconstriction curve due to administration of single dose of noradrenaline bitartrate or KCl were observed when constriction curve became stable. ② Changes of amplitude of constriction of ventricular papillary muscular induced by electro-stimulation: Electro-stimulation was used to stimulate the ventricle papillary muscular synchronized constriction with the frequency of once per second, wavelength of 3 ms and threshold voltage of 120%; when constriction curve became stable, DL or nimodipine was administered in a accumulative way. MAIN OUTCOME MEASURES: ① Constriction intensity of basilar artery, thoracic aorta and papillary muscle of ventricle in vitro. ② Influence of DL or nimodipine on the half-effective concentration of noradrenaline bitartrate or KCl that contributed to the vascular ring constriction of rabbit. RESULTS: Basilar artery, thoracic aorta and ventricular papillary muscle were obtained from 46 rabbits, and all data were statistically analyzed. ① Resting tension of basilar artery was increased by DL but decreased by nimodipine, and they exerted no influence on thoracic aorta. ② Constriction of basilar artery and thoracic aorta induced by noradrenaline bitartrate and KCl can be relaxed by DL in a dose dependant manner, and the half-effective concentration was (6.69±3.12)×10-4, (3.41±1.52)×10-3 mmol/L for basilar artery, and (1.49±0.59)×10-3, (2.91±0.99)×10-3 mmol/L for thoracic aorta, displaying stronger inhibition on the constriction of basilar artery induced by noradrenaline bitartrate than on the contraction induced by KCl. On the contrary, nimodipine showed stronger depression on KCl-induced constriction than on the constriction induced by noradrenaline bitartrate. ③ Noradrenaline bitartrate or nimodipine can depress the constriction of ventricle papillary muscular induced by electro-stimulation in a dose-dependant manner, and the half-effective concentration of DL on the contraction of ventricle papillary muscle induced by electro-stimulation was significantly higher than that induced by noradrenaline bitartrate. CONCLUSION: DL displays obvious selective effect on basilar artery of rabbit, the possible existence of constrictive α1 receptor subtype and dilating β receptor on basilar artery might be correlated with the selective function of DL, which benefit, for the improvement of blood supply in the ischemic region.更多还原