植物雌激素α-玉米赤霉醇内皮依赖性舒张效应的机制研究

目的探讨植物雌激素α-玉米赤霉醇(α-ZAL)对大鼠胸主动脉环内皮依赖性舒张效应中一氧化氮合酶(NOS)-NO-环磷酸鸟苷(cGMP)系统的作用。方法采用体外血管环灌流的方法,先用10-6mol/L苯肾上腺素预收缩血管。观察10-10～10-5mol/L6个不同浓度α-ZAL对内皮完整和去除内皮的大鼠胸主动脉环的舒张作用。α-ZAL10-10～10-8mol/L为低浓度组,α-ZAL10-7～10-5mol/L为高浓度组,0.1%乙醇浓度为对照组。在高浓度组中分别预先加用10-5mol/L左旋硝基精氨酸甲酯(L-NAME组)和亚甲蓝(MB组)并观察其影响,测定动脉环中内皮型一氧化氮合酶(eNOS)和cGMP含量及灌流液中NO含量变化。结果L-NAME组和MB组均可减弱高浓度组中α-ZAL的内皮依赖性胸主动脉环舒张作用(P<0.05,P<0.01);与对照组比较,高浓度组胸主动脉环中eNOS、cGMP含量及灌流液中NO含量增高(P<0.05,P<0.01);与高浓度组比较,L-NAME组可降低灌流液中NO含量及胸主动脉环中cGMP含量(P<0.05,P<0.01);MB组可降低胸主动脉环中cGMP含量(P<0.01)。结论α-ZAL的内皮依赖性舒张作用与NOS-NO-cGMP系统的激活有关。

Study on mechanism of endothelium-dependent vasodilating effect of phytoestrogen α-zearalanol

Objective To explore the possible mechanisms involved in endothelium-dependent dilating effect of phytoestrogen α-zearalanol(α-ZAL)on rat thoracic aortas.Methods Intact or endothelium-denuded thoracic aorta rings were put in individual organ chamber to observe the endothelium-dependent vasodilating effects of α-ZAL(10-10-10-5mol/L).The aorta rings were pre-contracted by phenylephrine(10-6 mol/L).The relaxing effects of α-ZAL were determined and the influence of Nω-nitro-L-arginine methylester(L-NAME,nitric oxide synthase inhibitor)and methylene blue(MB,guanylate cyclase inhibitor)was observed.The contents of endothelial nitric oxide synthase(eNOS)and cyclic guanosine monophosphate(cGMP)in aorta tissues and the content of nitric oxide(NO)in perfusate were detected.Results α-ZAL induced endothelium-dependent vasodilating effect on intact thoracic aortas.This vasodilation was inhibited either by L-NAME or by MB.α-ZAL could increase the content of eNOS,cGMP and NO.L-NAME could decrease the content of cGMP and NO;MB could decrease the content of cGMP.Conclusion The activation of NOS-NO-cGMP system is involved in the endothelium-dependent vasodilating effect of phytoestrogen α-ZAL.