度洛西汀对大鼠胸主动脉环舒张功能的影响

摘要

目的 研究度洛西汀(DLX)对血管舒张功能的影响并探讨其作用机制.方法 采用离体血管环灌流装置,观察DLX对大鼠胸主动脉环的作用及不同工具药的影响.结果 DLX对KCl(30 mmol·L-1)和NE(1 μmol·L-1)预收缩的血管环具有浓度依赖的舒张作用，对内皮完整和去内皮血管环舒张作用无差异，该舒张作用为非内皮依赖性.在KCl预收缩基础上，加入钾通道阻断剂格列苯脲Gli (10 μmol·L-1)、四乙胺TEA (10 mmol·L-1)、氯化钡BaCl2(1 mmol·L-1)、四氨基吡啶4-AP (1 mmol·L-1) 和5-HT2受体阻断剂赛庚啶(1 μmol·L-1) 均不能抑制DLX的舒血管效应;α1受体阻断剂哌唑嗪(1 μmol·L-1)组对DLX舒血管作用有抑制作用.在无钙液中，DLX可以明显抑制NE和CaCl2收缩血管的作用.结论 DLX能够浓度依赖性的舒张血管，其机制可能与抑制经由血管平滑肌细胞膜VDC和ROC通道的钙离子内流，拮抗α1受体以及抑制胞质内钙离子释放有关.%Aim To investigate the effect of duloxetine DLX )on vasodilatation of rat aortic rings and the mechanism. Methods The isolated thoracic aortic rings of male Wistar rats were mounted on the organ bath and tension was recorded isometrically. The effect of DLX on the rings with endothelium intact or endothelium denuded precontracted by the potassium chloride ( KCl, 30 mmol ·L-1 ) or norepinphrine( NE, 1 μmol · L-1 ), and the effect of DLX on the vessel reaction induced by various drugs were recorded with biological signal analytical system. Results DLX completely relaxed the contractions induced by KCl and NE in a concentration-dependent manner in endotheliumintact and endothelium-denuded rat aorta. The vasodilator effect of DLX was not statistically inhibited by glibenclamide ( Gli, 10 μmol · L-1 ). tetraethtylamine ( TEA. 10 mmol · L-1 ), barium chloride ( BaCl2 , 1 mmol · L-1 ).4-aminopyridine ( 4-AP,1 mmol · L-1 )and cyproheptadine( 1 μmol · L-1 ) in KCl pre-contracted thoracic aortic rings . The vasodilator effect of DLX was partially inhibited by prazosin ( I μmol · L-1 ). DLX could significantly inhibit the contraction induced by additions of NE in Ca2+-free PSS, and the contraction induced by additions of CaCl2. Conclusion DLX-induced vasodilatation is mainly related to blocking α1-adrenoceptor, and interfering intracellular calcium homeostasis by blocking Ca2+ influx and intracellular Ca2+ release.