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

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

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。

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 endo- thelium denuded thoracic aorta rings were put in individual organ chamber to observe the endo- thelium-dependent vasodilating effects of α-ZAL（10^-10 -10^-5 mol/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 Nm-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.