麻黄与杏仁配伍后在支气管哮喘模型大鼠体内的药动学研究  

Pharmacokinetic study of the complication of Ephedra sinica and Prunus armeniaca in bronchial asthma model rats

作　　者：陈林林 谢金根 樊学程 饶倩 杨添翼 田佳玉 肖雄[1] 高文军[1] 李文宏[1] CHEN Linlin;XIE Jingen;FAN Xuecheng;RAO Qian;YANG Tianyi;TIAN Jiayu;XIAO Xiong;GAO Wenjun;LI Wenhong(School of Pharmacy,Jiangxi University of Chinese Medicine,Nanchang 330004,China)

机构地区：[1]江西中医药大学药学院,南昌330004

出　　处：《中国药房》2024年第13期1588-1593,共6页China Pharmacy

基　　金：国家自然科学基金项目(No.82060790,No.82360856);江西省自然科学基金资助项目(No.20202ACBL206031)。

摘　　要：目的 研究麻黄与杏仁配伍后在支气管哮喘模型大鼠血浆和脑脊液中的药动学变化。方法 将SD雄性大鼠随机分为空白组、模型组、麻黄组(12 g/kg,以生药量计,下同)、杏仁组(6 g/kg)和麻黄-杏仁药对组(麻黄12 g/kg+杏仁6 g/kg),每组6只。除空白组外,其余各组大鼠用2%氯化乙酰胆碱和0.4%磷酸组胺的等体积混合液喷雾诱发支气管哮喘模型,每天1次,连续7 d。每次造模前1 h,各组大鼠灌胃相应药物/生理盐水,每天1次,连续7 d。末次给药并激发哮喘后,分别在不同时间点进行采血和脑脊液收集。将血浆与脑脊液样品预处理后(以葛根素为内标),采用液相色谱-串联质谱法检测两种样品中麻黄碱/伪麻黄碱、甲基麻黄碱和苦杏仁苷的质量浓度。采用DAS 2.0药动学软件通过非房室模型确定主要药动学参数,并比较两药配伍前后药动学参数的变化。结果 与麻黄组比较,麻黄-杏仁药对组大鼠血浆和脑脊液中麻黄碱/伪麻黄碱、甲基麻黄碱的c_(max)、AUC_(0-21.33 h)(或AUC_(0-10.67 h))均显著减少,CL_(Z)/F、V_(Z)/F均显著增加(P<0.05或P<0.01);脑脊液中甲基麻黄碱的t_(max)显著缩短(P<0.05)。与杏仁组比较,麻黄-杏仁药对组大鼠血浆中苦杏仁苷的t_(1/2)显著缩短,CL_(Z)/F显著增加(P<0.01);脑脊液中苦杏仁苷的t_(max)显著缩短,AUC_(0-10.67 h)、CL_(Z)/F、V_(Z)/F均显著增加(P<0.01)。结论 麻黄、杏仁配伍后加快了麻黄生物碱的吸收和消除,从而减少了麻黄生物碱在支气管哮喘模型大鼠体内的累积。OBJECTIVE To study the pharmacokinetic changes in the plasma and cerebrospinal fluid of bronchial asthma model rats after the complication of Ephedra sinica and Prunus armeniaca.METHODS SD male rats were randomly divided into blank group,model group,E.sinica group(12 g/kg,calculated by raw drug,similarly hereinafter),P.armeniaca group(6 g/kg)and E.sinica-P.armeniaca drug-pair group(12 g/kg of E.sinica+6 g/kg of P.armeniaca),with 6 rats in each group.Except for the blank group,the bronchial asthma model was induced by spraying rats in each group with an equal volume mixture of 2%acetylcholine chloride and 0.4%histamine phosphate,once a day,for 7 d.One hour before modeling every time,rats in each group were gavaged with the corresponding drug/normal saline,once a day,for 7 d.After the final administration and provocation of asthma,blood and cerebrospinal fluid collection were performed at different time points.The plasma and cerebrospinal fluid samples were pre-treated(with geranylgeranyl as the internal standard),and the mass concentrations of ephedrine/pseudoephedrine,methyl ephedrine and amygdalin in both samples were determined by liquid chromatography-tandem mass spectrometry.DAS 2.0 pharmacokinetic software was used to determine the main pharmacokinetic parameters through the non-atrial chamber model and to compare the changes of the pharmacokinetic parameters before and after the combination of the two drugs.RESULTS Compared with E.sinica group,c_(max) and AUC_(0-21.33 h)(or AUC_(0-10.67 h))of ephedrine/pseudoephedrine and methyl ephedrine in the plasma and cerebrospinal fluid of rats were significantly reduced in E.sinica-P.armeniaca drug-pair group,while CL_(Z)/F and V_(Z)/F were significantly increased(P<0.05 or P<0.01);t_(max) of methyl ephedrine in the cerebrospinal fluid was significantly shortened(P<0.05).Compared with P.armeniaca group,the t_(1/2) of amygdalin in the plasma of rats in E.sinica-P.armeniaca drug-pair group was significantly shortened,and CL_(Z)/F was significantly increased(P<0.01);the

关 键 词：麻黄 杏仁 配伍 哮喘 药动学 

分 类 号：R969.1[医药卫生—药理学]