基于代谢物组麻杏石甘汤止喘量效关系的实验研究

Experimental Study of Dose-effect Relationship of Maxing Shigan Decoction in Relieving Asthma Based on Metabonomics Overall Effect

目的应用代谢物组整体效应评价麻杏石甘汤对哮喘动物治疗作用的量效关系。方法取110只豚鼠随机分为空白组,模型组,麻杏石甘汤剂量1-9组,每组10只。除空白组外,其余各组用2%氯化乙酰胆碱＋0.4%磷酸组胺复制哮喘模型,造模前麻杏石甘汤各剂量组分别给予0.90,1.33,2.00,3.00,4.50,6.75,10.13,15.19,22.78 g·kg^-1的麻杏石甘汤,空白组和模型组给予等量蒸馏水。造模30 min后,心脏采血,血浆预处理后,HPLC/MS/MS检测血浆中物质,PCA分析麻杏石甘汤的整体效应,Prism 5.0拟合其量效关系函数。结果基于代谢物组整体效应麻杏石甘汤量效函数Y=-5.32＋17.96/（1＋10^（（0.15-X）×-8.8））,拟合度0.86,中位剂量[D]0.5=1.33 g·kg^-1。量效剂量范围：[D]0.2-[D]0.8=1.132-1.551 g·kg^-1,阈剂量：1.132 g·kg^-1。结论代谢物组可作为中药复方整体效应评价指标,为研究中药复方量效关系提供一种新的思路。

Objective To investigate the dose-effect relationship of of Maxing Shigan Decoction（MSD）in relieveing guinea pis asthma on the basis of metabonomics overall effect. Methods One hundred and ten guinea pigs were evenly randomized into 11 groups, namely normal control group, model group and MSD groups 1-9. Guinea pigs except for the normal control group were given atomization inhalation of 2 % acetylcholine chloride＋0.4 % histamine phosphate to induce asthma. Before modeling,the guinea pigs of MSD groups 1-9 were given 0.90,1.33,2.00,3.00, 4.50,6.75, 10.13, 15.19, 22.78 g·kg^-1of MSD, and those in the normal control group and model group were given distilled water. Thirty minutes after modeling, blood was sampled from the heart, and endogenous compounds in the blood were analyzed by HPLC-MS-MS after plasma pretreatment, the overall effect of MSD was analyzed by PCA,and the dose-effect curve was fitted by prism 5.0. Results The dose-effect function of MSD based on overall effect of metabonomics was Y =-5.32＋17.96/（1＋10^（（0.15-X）×-8.8））,R2=0.86,and the mediam dosage [D]0.5was 1.33 g·kg^-1.The related parameters were as follows： Effective dose range [D]0.2-[D]0.8being 1.132 g·kg-1-1.551 g·kg^-1, and threshold dose [D]0.2being 1.132 g·kg^-1. Conclusion The metabonomics could be used as an evaluation index for the overall effect of traditional Chinese medicine（TCM）and will provide a novel way to study the dose-effect relationship of TCM.