咳喘膏穴位贴敷对哮喘豚鼠氨茶碱药代动力学影响的研究

Effect of acupoint application of Kechuan plaster on pharmacokinetics of aminophylline in asthmatic guinea pigs

[目的]研究中药咳喘膏穴位贴敷对哮喘豚鼠氨茶碱药代动力学的影响,探讨其可能机制。[方法]将30只豚鼠随机分为5组,分别为正常组、模型组、咳喘膏高、中、低剂量组,每组6只。采用卵蛋白致敏-雾化激发方法复制豚鼠支气管哮喘模型。豚鼠均予氨茶碱灌胃,咳喘膏高、中、低剂量组予咳喘膏穴位贴敷,按设定时点经豚鼠内眦取血,高效液相色谱法检测氨茶碱血药浓度,DAS2.0药代动力学软件计算氨茶碱药代动力学参数。[结果]咳喘膏高剂量组与正常组、模型组及低剂量组比较,氨茶碱半衰期(T1/2)延长(P=0.007,P=0.022,P=0.028)、消除速率常数(Ke)减低(P=0.005,P=0.012,P=0.015),差异有统计学意义;咳喘膏中剂量组与正常组比较,氨茶碱T1/2延长(P=0.029)、Ke减低(P=0.047),差异有统计学意义。[结论]咳喘膏穴位贴敷可影响氨茶碱药代动力学,使氨茶碱T1/2延长,Ke减低。可以通过调控咳喘膏药物颗粒直径的方法,减小咳喘膏穴位贴敷对氨茶碱药代动力学影响。

[Objective] To investigate the effect of acupoint application of Kechuan plaster on pharmaeokinetics of aminophylline in asth- matic guinea pigs, and to explore its possible mechanism. [Methods] The 30 guinea pigs were assigned to 5 groups randomly, respectively as the normal group, model control group, Kechuan plaster high dose group, medium dose group and low dose group, 6 guinea pigs in each group. Except the normal group, all the other 4 groups were injected into the abdominal cavity with OVA to induce allergy reaction, then inhaled OVA for excitation to prepare the asthma model groups. All guinea pigs were fed aminophylline by garage, Kechuan plaster high, medium and low dose group was treated with Kechuan plaster acupoint application according to different dosage. Blood was taken by inner canthus puncture, according to the set time point. Plasma concentration of aminophylline was detected by HPLC. DAS2.0 software was used to calculate the pharmacokinetics parameters of aminophylline. [Results] Compared with normal group , model control group and low dose group, plasma half-life of aminophylline extended （P=0.007, P=0.022, P=0.028 ）and elimination rate constant decreased （P= 0.005, P=0.012, P=0.015 ） in high dose group. Compared with normal group, plasma half-life of aminophylline extended （P=0.029） and elimination rate constant decreased （P=0.047）in medium dose group. [Conclusion] Kechuan plaster acupoint application can affect the phannacokinetics of aminophylline, and it can extend the plasma half-life and decrease the elimination rate constant. The effect of Kechuan plaster could be controlled by changing the drug particles＇ diameter.