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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
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| 篇名： | 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 |
| TITLE： | Pharmacokinetic study of the complication of Ephedra sinica and Prunus armeniaca in bronchial asthma model rats |
| 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（12g/kg，以生药量计，下同）、杏仁组（6g/kg）和麻黄-杏仁药对组（麻黄12g/kg+杏仁6g/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7d。每次造模前1h，各组大鼠灌胃相应药物/生理盐水，每天1次，连续7d。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DAS2.0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cmax、AUC0-21.33（h或AUC0-10.67h）均显著减少，CLZ/F、VZ/F均显著增加（P＜0.05或P＜0.01）；脑脊液中甲基麻黄碱的tmax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t1/2显著缩短，CLZ/F显著增加（P＜0.01）；脑脊液中苦杏仁苷的tmax显著缩短，AUC0-10.67h、CLZ/F、VZ/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。 |
| ABSTRACT： | 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， cmax and AUC0-21.33 h （or AUC0-10.67 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 CLZ/F and VZ/F were significantly increased （P＜0.05 or P＜0.01）； tmax of methyl ephedrine in the cerebrospinal fluid was significantly shortened （P＜ 0.05）.Compared with P. armeniaca group， the t1/2 of amygdalin in the plasma of rats in E. sinica-P. armeniaca drug-pair group was significantly shortened， and CLZ/F was significantly increased （P＜0.01）； the tmax of bitter amygdalin in the cerebrospinal fluid was significantly shortened， and the AUC0-10.67 h， CLZ/F， and VZ/F were significantly increased （P＜0.01）. CONCLUSIONS The combination of E. sinica and P. armeniaca accelerates the absorption and elimination of ephedra alkaloids， thus reducing the accumulation of ephedra alkaloids in the bronchial asthma model rats. |
| 期刊： | 2024年第35卷第13期 |
| 作者： | 陈林林；谢金根；樊学程；饶倩；杨添翼；田佳玉；肖雄；高文军；李文宏 |
| AUTHORS： | CHEN Linlin， XIE Jingen，FAN Xuecheng，RAO Qian，YANG Tianyi，TIAN Jiayu，XIAO Xiong，GAO Wenjun，LI Wenhong |
| 关键字： | 麻黄；杏仁；配伍；哮喘；药动学 |
| KEYWORDS： | Ephedra sinica； Prunus armeniaca； complica- |
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