基于含药肝孵育液法的麻黄-杏仁药对舒张支气管平滑肌的β2受体机制与效应成分验证  

Validation ofβ-receptor mechanism and effector components of ephedra-almond drug on diastolic bronchial smooth muscle based on drug-containing liver incubation solution method

作　　者：李文宏[1] 樊学程 谢金根 陈林林 雷婷 饶倩 肖雄[1] 高文军[1] LI Wen-hong;FAN Xue-cheng;XIE Jin-gen;CHEN Lin-lin;LEI Ting;RAO Qian;XIAO Xiong;GAO Wenjun(School of Pharmacy,Jiangxi University of Chinese Medicine,Jiangxi Nanchang 330004,China)

机构地区：[1]江西中医药大学药学院,江西南昌330004

出　　处：《中国医院药学杂志》2023年第10期1078-1083,共6页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金项目(编号:82060790);江西省自然科学基金项目(编号:20202ACBL206031);2021年江西中医药大学校级研究生创新基金项目(编号:JZYC21S31)。

摘　　要：目的:分析麻黄-杏仁药对含药肝孵育液的解痉效应成分与效应指标之间的关联性,与分子对接及文献结果对比,进一步探讨含药肝孵育液法用于中药体外组织器官水平药理学研究的可行性。方法:采用HPLC法测定麻黄-杏仁药对含药肝孵育液中麻黄碱(X1)、伪麻黄碱(X2)、甲基麻黄碱(X3)、苦杏仁苷(X4)的含量;于乙酰胆碱和磷酸组胺预收缩的离体气管环痉挛模型,采用生物信号采集系统检测气管环张力变化,ELISA检测气管组织环磷酸腺苷(cAMP)与环磷酸鸟苷(cGMP)及二者比值变化;采用多元线性回归分析效应成分与效应指标的相关性;采用分子对接技术分析验证上述实验结果。结果:麻黄-杏仁药对能上调气管环舒张率(Y1)和cAMP/cGMP比值(Y2);以效应成分含量为自变量,效应指标变化为因变量,得回归方程分别为Y1=0.238 X1-0.105 X2+0.675 X3-0.097 X4-82.161(R2=0.961)和Y2=0.093 X1-0.056 X2+0.108 X3+0.017 X4-16.197(R2=0.999),效应成分与效应指标之间相关性较强,其对效应指标影响程度为:甲基麻黄碱>麻黄碱>伪麻黄碱>苦杏仁苷;分子对接结果表明效应成分与肾上腺素β2受体的结合程度与上述结果一致。结论:麻黄-杏仁药对含药肝孵育液用于体外支气管环的药效结果与分子对接及文献调研结果基本一致,进一步表明该方法用于中药体外组织器官水平药效学研究具有一定的可行性。OBJECTIVE By analyzing the correlation between the antispasmodic effect components and indexes of ephedra-almond drug on drug-containing liver incubation solution,the feasibility of the drug-containing liver incubation solution method for in vitro pharmacological studies of Chinese medicine at the tissue and organ level was initially investigated by comparing with molecular docking and literature results.METHODS The contents of ephedrine(X1),pseudoephedrine(X2),methylephedrine(X3)and amygdalin(X4)in the drug-containing liver incubation solution of drug pair were determined by HPLC method.In an isolated tracheal ring spasm model precontracted with acetylcholine and histamine phosphate,a biosignal acquisition system was used to detect the changes in tracheal ring tension,and ELISA detection of cyclic adenosine monophosphate(cAMP)and cyclic guanosine monophosphate(cGMP)in tracheal tissue and changes in the ratio of the two.Multiple linear regression was used to analyze the correlation between effect components and effect indicators.The above experimental results are confirmed with the results of molecular docking technology analysis.RESULTS The ephedra-almond drug pair could significantly increase the tracheal ring relaxation rate(Y1),and up-regulate the cAMP/cGMP ratio(Y2)in the tissue.Taking the content of the effect components as the independent variable and the change of the effect index as the dependent variable,the regression equations were Y1=0.238 X1-0.105 X2+0.675 X3-0.097 X4-82.161(R2=0.961)and Y2=0.093 X1-0.056 X2+0.108 X3+0.017 X4-16.197(R2=0.999),the correlation between effect components and effect indicators is strong and the degree of influence on the effect indexes was:methylephedrine>ephedrine>pseudoephedrine>amygdalin.The molecular docking results showed that the binding degree of effector components to the adrenergic beta 2 receptor was consistent with the above results.CONCLUSION The pharmacodynamic results of ephedra-almond drug-containing liver incubation solution for in vitro bronchial ring we

关 键 词：含药肝孵育液法 体外药理学研究 麻黄-杏仁药对 效应成分 

分 类 号：R966[医药卫生—药理学] R285[医药卫生—药学]