芹菜素舒张血管作用及其机制研究  

Endothelium-dependent vasorelaxation effects induced by apigenin on the thoracic aorta of rats and its possible mechanism

作　　者：隋海霞[1] 支媛[1] 刘海波[1] 高芃[1] 徐海滨[1] 严卫星[1] 

机构地区：[1]中国疾病预防控制中心营养与食品安全所,北京100021

出　　处：《卫生研究》2011年第4期416-419,422,共5页Journal of Hygiene Research

基　　金：国家科技支撑计划项目(No.2006BAK02A07)

摘　　要：目的研究芹菜素的舒血管作用及机制。方法大鼠胸主动脉环张力测定法。腹腔注射1%戊巴比妥钠麻醉大鼠,迅速游离大鼠胸主动脉,剪成3～4mm的血管环。血管环悬挂于20ml 95%O2和5%CO2饱和的37℃Kreb液中,以BIO-PAC MP150系统记录血管环张力,研究芹菜素对苯肾上腺素(phenylephrine,PE)预收缩主动脉环张力的作用、各种内皮阻断剂对芹菜素舒张血管作用的影响、钾通道阻断剂对芹菜素舒张血管作用的影响以及芹菜素舒张血管与钙通道的关系。结果芹菜素不影响血管环的静息张力。芹菜素在有或无内皮的血管环上均可剂量依赖性地减小苯肾上腺素(PE)预收缩的血管张力,但是在内皮完整的血管环上,这一作用显著大于去内皮血管环(P<0.05)。用L-N-硝基精氨酸甲酯(L-NAME)、亚甲蓝(MB)孵育内皮完整的血管环后,可明显抑制芹菜素引发的血管舒张,与未经处理的内皮完整血管环组相比有显著性差异(P<0.05)。而预先给予吲哚美辛并不能抑制芹菜素引发的血管舒张作用。4-氨基吡啶(4-AP)、5-羟基癸酸(5-HD)、四乙氨(TEA)、氯化钡(BaCl2)均能显著抑制芹菜素对PE预收缩去内皮血管环的舒张作用(P<0.05)。在无钾环境下,芹菜素对PE引起的血管环收缩有显著抑制作用(P<0.05)。芹菜素对高钾引起的血管环收缩也具有显著的抑制作用(P<0.05)。无钙环境下,芹菜素可显著降低加入Ca2+引起的血管张力的升高(P<0.05)。结论芹菜素具有显著的舒血管作用,其机制涉及到NO介导的信号传导途径,与抑制电压依赖性钙通道、受体操纵性钙通道以及细胞外钙内流受抑和钾通道激活有关。Objective To investigate the vasorelaxant effect and mechanism of apigenin.Methods Rats were anesthetized with 1% sodium pentobarbital（i.p.） and killed by exsanguination.The thoracic aorta was isolated and cut into 3-4 mm rings and suspended in an organ bath filled with 20 ml Kreb solution which was maintained at 37℃ and ventilated continuously with 95% O2 and 5% CO2.The contraction was measured with a multichannel acquisition and analysis system（BIO-PAC MP150,America）.Related studies were conducted on the effect of apigenin on the contraction induced by phenylephrine（PE） and role of endothelium,K＋ channel as well as Ca2＋ channel in PE-induced relaxation.Result Apigenin had no effect on the basal tension in rat aortic rings.Apigenin can relax PE pre-contracted rings in both endothelium-intact aortic and endothelium-denuded aortic in a dose-dependent manner,with the effect of endothelium-intact aortic significantly stronger than that of endothelium-denuded aortic（P0.05）.Pre-incubation of endothelium-intact rings with L-NAME and methylene blue significantly reduced apigenin-induced relaxation（P0.05）.However,indomethacin did not significantly affect the apigenin-induced relaxation in endothelium-intact rings（P0.05）.4-AP,5-HD,TEA as well as BaCl2 significantly inhibited apigenin-induced relaxation in endothelium-denuded rings pre-contracted by PE（P0.05）.In the K＋-free solution,apigenin can significantly inhibit PE pre-contracted aortic rings（P0.05）.In the Ca2＋-free solution plus PE,cumulative addition of CaCl2 induced a stepwise tension increase of aortic rings.Pretreated with apigenin significantly attenuated CaCl2 induced contraction.Conclusion Apigenin induces both endothelium-dependent and independent relaxation.NO and cGMP are involved in the endothelium-dependent relaxation,inhibition of voltage-dependent or receptor-operate Ca2＋ channel or extracellular Ca2＋ influx and activation of K＋ channel contribute in part to the endothelium-independent relaxation by apigen

关 键 词：芹菜素 主动脉 血管 一氧化氮 钙通道 

分 类 号：R544.1[医药卫生—心血管疾病] Q946[医药卫生—内科学]