咪达唑仑对离体猪冠脉环舒张功能的影响及其机制研究

发布时间：2018-03-14 13:45

本文选题：咪达唑仑　切入点：猪冠状动脉环　出处：《中国药理学通报》2017年08期 　论文类型：期刊论文

【摘要】：目的本实验观察咪达唑仑(midazolam)对离体猪冠状动脉环的作用,并探讨其作用机制。方法采用离体血管张力测定实验方法,记录咪达唑仑对KCl(30 mmol·L~(-1))预收缩猪冠状动脉环张力的变化及不同工具药的影响。结果各浓度组咪达唑仑(3×10~(-6)~1×10~(-4)mol·L~(-1))对预收缩猪冠脉环产生浓度依赖性舒张作用,内皮完整组舒张作用强于去内皮组(P0.05);在KCl预收缩基础上,加入NOS抑制剂L-NAME、L-NAME+L-Arg后,咪达唑仑舒血管作用明显减弱(P0.05),而加入外源性的NO合成底物L-Arg、i NOS抑制剂1400W、环氧合酶抑制剂Indo均不能抑制咪达唑仑的舒血管作用;Na~+/Ca~(2+)交换体特异性阻断剂KBR7943亦不能抑制咪达唑仑的舒血管作用;钾通道阻断剂K_(ATP)阻断剂Gli可以抑制咪达唑仑的舒张冠脉作用(P0.05),BKCa阻断剂TEA、Kir阻断剂Ba Cl2、KV阻断剂4-AP则不能改变咪达唑仑的舒张冠脉作用。结论咪达唑仑可浓度和内皮依赖性地舒张KCl预收缩的猪冠脉环,内皮分泌的NO参与了其舒血管作用,外源性NO、i NOS以及PGI2的合成与其舒血管作用无关,咪达唑仑对猪冠脉的舒张可能与K_(ATP)通道有关,与Na~+/Ca~(2+)交换体、K_V通道、BK_(Ca)通道、K_(ir)通道无关。
[Abstract]:Objective to observe the effect of midazolam on isolated porcine coronary rings and its mechanism. The effects of midazolam on the changes of coronary artery ring tension and the effects of different drugs on the coronary artery ring tension of KCl(30 mmol 路L ~ (-1) were recorded. Results midazolam 3 脳 10 ~ (-1) -4 渭 mol 路L ~ (-1) of midazolam had a concentration-dependent relaxation effect on precontracted porcine coronary rings. The vasodilation effect in the intact endothelial group was stronger than that in the deendothelium-free group, and on the basis of KCl precontraction, L-NAME L-Arg, a NOS inhibitor, was added. Midazolam significantly weakened the vasostatic effect of P0.05N, and neither did the cyclooxygenase inhibitor Indo (Indo) inhibit the vasodilation of midazolam by adding an exogenous no synthesis substrate, L-Argor NOS inhibitor 1400W, nor did KBR7943, an exchanger-specific blocker. Can inhibit midazolam vasodilation effect; Potassium channel blocker Gli can inhibit the diastolic effect of midazolam. Conclusion the concentration of midazolam and the endothelium of midazolam can not be changed by BaCl2 + KV blocker 4-AP, which can inhibit the diastolic effect of midazolam. Lycidal relaxation of KCl precontracted porcine coronary rings, The synthesis of exogenous Nov NOS and PGI2 was not related to vasodilation. Midazolam's relaxation to porcine coronary artery might be related to the K ~ / / Ca ~ (2 +) channel, but not to the Na ~ / / Ca ~ / Ca ~ (2)) exchanger.
【作者单位】：山西医科大学第一医院内科学教研室;山西医科大学药理学教研室;山西医科大学第一医院药学部;
【基金】：山西省研究生教育创新项目(No 2016BY077) 山西医科大学青年基金(No 02201514)
【分类号】：R965

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