西红花酸部分内皮依赖性血管舒张作用及其机制

Partial endothelium-dependent vasorelaxation of crocetin and its mechanism

目的:研究西红花酸(crocetin,CCT)血管舒张作用及其可能机制。方法:采用RM6240C型多道生物信号采集处理系统,记录灌流大鼠胸主动脉环张力变化。结果:CCT(10-9~10-4mol/L)对苯肾上腺素(PE,10-5mol/L)预收缩的内皮完整血管环产生浓度依赖性的舒张作用;CCT(3×10-9~10-4mol/L)对苯肾上腺素(PE,10-5mol/L)预收缩的去内皮血管环产生浓度依赖性的舒张作用,但内皮完整组血管舒张作用比去内皮组更明显,两者相比,在10-8~10-4mol/L时,具有显著性差异(P<0.01)。CCT对高浓度KCl(6×10-2mol/L)预收缩的血管环无明显的舒张作用。一氧化氮合酶抑制剂左旋硝基精氨酸甲酯(10-4mol/L)或前列环素合成酶抑制剂吲哚美辛(10-5mol/L)预处理,对CCT诱导的内皮完整动脉环舒张作用具有明显的抑制效应。ATP敏感性K+通道阻断剂格列苯脲(3×10-6mol/L)预处理后,CCT的舒血管作用均无显著变化(P>0.05),但Ca2+激活K+通道抑制剂四乙胺(5×10-3mol/L)或电压敏感性K+通道抑制剂4-氨基吡啶(10-3mol/L)预处理,可明显减弱CCT引起的无内皮血管舒张作用(P<0.01)。结论:CCT对大鼠胸主动脉具有部分内皮依赖性舒张作用,其内皮依赖性血管舒张作用的机制,与其促进内皮一氧化氮合酶或环氧合酶途径,从而增加一氧化氮和前列环素的生成有关;其内皮非依赖性舒血管效应的作用机制涉及Ca2+激活K+通道或电压敏感型K+通道的激活。

Objective: To investigate the vasorelaxation effect of crocetin(CCT) and its mechanism.Methods: Isolated aortic rings from Sprague-Dawley rats were mounted in the organ bath system.The tension of the aorta was recorded.Results: CCT significantly provoked concentration-dependent relaxation in both endothelium-intact and-denuded aortic rings pre-constricted by phenylephrine(10-5 mol/L),and the vasorelaxation in endothelium-intact aortic rings was stronger than that in endothelium-denuded ones.CCT had no significant effects on aortic rings pre-constricted with KCl(6×10-2 mol/L).Pretreatment with eith L-NAME(10-4 mol/L),an inhibitor of nitric oxide synthase(NOS),or indomethacin(10-5 mol/L),an inhibitor of cyclooxygenase,for 30 min significantly attenuated the relaxation of endothelium-intact aortic rings induced by CCT.Besides,both tetraethylammonium(a Ca2+-activated K+ channel inhibitor,5×10-3 mol/L) and 4-aminopyridine(a voltage-sensitive K+ channel inhibitor,10-3 mol/L),but not the ATP-sensitive K+ channel inhibitor glibenclamide(3×10-6 mol/L),significantly attenuated CCT-induced relaxation in endothelium-denuded aortic rings.Conclusion: CCT had partial endothelium-dependent relaxation in rat aortas,which may be mediated by activating the endothelial NOS-NO and cyclooxygenase-prostacyclin pathways.The endothelium-independent relaxation in rat aortas induced by CCT may be mediated by Ca2+-activated K+ channels and voltage-sensitive K+ channels.