论文部分内容阅读
目的:研究川阿格雷钠(MC-002)对大鼠胸主动脉的舒张作用,并探讨其可能的作用机制。方法:测定川阿格雷钠对去甲肾上腺素(NE)和高钾预收缩的大鼠胸主动脉血管环的舒张作用,并观察L-硝基精氨酸甲酯(L-NAME)、亚甲蓝、吲哚美辛、格列本脲、蜂毒明肽、氯化钡和4-氨基吡啶对其作用的影响。结果:川阿格雷钠(3～300μmol/L)能浓度依赖性地舒张NE预收缩的完整血管环,去内皮、亚甲蓝孵育和吲哚美辛孵育均能显著抑制其舒血管作用(P<0.05,P<0.01),L-NAME孵育无显著影响。川阿格雷钠拮抗高钾诱导完整血管环收缩的作用被格列本脲(ATP敏感型钾通道KATP抑制剂)和蜂毒明肽(小传导性钙激活型钾通道SKCa抑制剂)显著降低(P<0.01),氯化钡和4-氨基吡啶无显著影响。川阿格雷钠使NE预收缩的血管平滑肌的钙浓度-收缩曲线下移、右移,且呈现浓度依赖性。结论:川阿格雷钠可能通过内皮细胞的鸟苷酸环化酶途径和环氧合酶途径、开放KATP和SKCa引起平滑肌细胞膜超极化以及减少钙内流而松弛血管。
Objective: To investigate the vasodilatory effect of chuanagrel (MC-002) on the thoracic aorta in rats and its possible mechanism. Methods: To determine the effect of chuanagrel on vasorelaxation of thoracic aorta in rats with norepinephrine (NE) and precontracted with high potassium, and to observe the effects of L-NAME, The effects of methylene blue, indomethacin, glyburide, bee venom peptide, barium chloride and 4-aminopyridine on their effects. Results: Chuanaguerre sodium (3 ~ 300μmol / L) could relax the intact vascular rings of NE precontracted in a concentration-dependent manner. Both endothelium, methylene blue incubation and indomethacin incubation could significantly inhibit the vasodilatation <0.05, P <0.01), L-NAME incubation had no significant effect. The effect of chuanagarrel on antagonizing high potassium induced intact ring contraction was significantly reduced by glyburide (a KATP inhibitor of the ATP-sensitive potassium channel) and bepidemin (a small-conduction calcium-activated potassium channel SKCa inhibitor) ( P <0.01), barium chloride and 4-aminopyridine had no significant effect. Chuanagrelide lowered and contracted the calcium concentration-contraction curve of NE pre-contracted vascular smooth muscle in a concentration-dependent manner. CONCLUSIONS: Chuanagrelide may relax blood vessels through the guanylate cyclase pathway and cyclooxygenase pathway of endothelial cells, opening of KATP and SKCa to cause hyperpolarization of smooth muscle cell membrane and decrease of calcium influx.