五味子醇甲对大鼠离体胸主动脉环作用研究

目的:研究五味子醇甲对大鼠离体胸主动脉环的舒张作用并探讨其可能机制。方法:应用离体血管环灌流模型观察五味子醇甲对大鼠胸主动脉环张力的作用,记录苯肾上腺素(PE,1×10-6mol/L)预收缩大鼠离体胸主动脉环的张力变化。采用一氧化氮合酶抑制剂左旋硝基精氨酸甲酯(L-NAME,3×10-4mol/L)、鸟嘌呤环化酶抑制剂1H-1,2,4]二唑4,3-α]喹喔啉-1-酮(ODQ,1×10-5mol/L)、环氧合酶抑制剂吲哚美辛(INDO,1×10-5mol/L)预孵后,观察五味子醇甲对血管张力变化的影响,并观察对PE诱发的内钙释放和Ca Cl2引起的外钙内流的影响。结果:在不改变基础张力的条件下,五味子醇甲对PE预收缩的内皮完整和去内皮大鼠离体胸主动脉环均有明显的舒张作用,差异有统计学意义(P<0.05)。预先用L-NAME、ODQ孵育后,五味子醇甲的舒张血管作用减弱,与对照组比较差异有统计学意义(P<0.05);用INDO孵育后,五味子醇甲的舒张血管作用较对照组无明显变化;且五味子醇甲对Ca Cl2引起的收缩有明显抑制作用。结论:五味子醇甲可浓度依赖性抑制由PE引起的血管收缩,并具有内皮依赖性和非内皮依赖性。内皮依赖性机制可能与一氧化氮-环磷酸鸟苷(NO-c GMP)途径有关,非内皮依赖性机制可能与抑制血管平滑肌上的受体依赖性钙通道,降低外钙内流有关。

Vasorelaxation Effect of Schisandrol A on Isolated Thoracic Aortic Rings in Rats

Objective:To investigate the effects of Schisandrol A on isolated thoracic aortic rings in Wistar rats and study the potential mechanism. Methods:Isometric tension recording was applied to evaluate the effect of cumulative Schisandrol A on endothelium-intact/denuded aorta rings under quiescent condition or pre-contracted with phenylephrine(PE,1×10-6 mol/L). The effect of Schisandrol A at the aforementioned doses on endothelium-intact aortic rings,pre-inhibited separately with the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester(L-NAME,3×10-4 mol/L),guanylate cyclase inhibitor(ODQ,1×10-5 mol/L),cyclooxygenase inhibitor indomethacin(INDO,1×10-5 mol/L),contracted with PE was also observed. And the effects of PE-induced Ca2+ release and Ca Cl2-induced Ca2+ influx were observed. Results:Under the condition of no change of resting tension,Schisandrol A had a significant effect on endothelium-intact and endothelium-denuded thoracic aortic rings which were pre-contracted with PE and there was statistical significance between the two groups(P< 0.05). Compared with the non-blocking group,there were statistical significance after incubation with L-NAME(P< 0.05) and ODQ(P< 0.05). The relaxation rate of the rings incubated with INDO was not statistical significance from that in the non-blocking group(P> 0.05). Schisandrol A obviously inhibited the contraction induced by Ca Cl2. Conclusions:Schisandrol A can inhibit the vasoconstriction caused by PE in a dose-dependent manner,and it was endothelium-dependent and non-endothelium-dependent. The endothelium-dependent mechanism may be related to the NO-c GMP pathway,and the non-endothelium-dependent mechanism may be associated with inhibition of receptor-dependent calcium channels on the vascular smooth muscle,which leads to the decrease of Ca2+influx.