中国中药杂志

2019, v.44(05) 1034-1040

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菌群失调大鼠体内PEG400对黄芩苷和黄芩素药代动力学的影响
Effect of PEG400 on pharmacokinetics of baicalin and baicalein in gut microbiotadysbiosis rats

顾腾;张硕;张敏;孟小夏;高秀丽;
GU Teng;ZHANG Shuo;ZHANG Min;MENG Xiao-xia;GAO Xiu-li;Pharmaceutical College,Guizhou Medical University;State Key Laboratory of Functions and Appliactions of Medical Plants,Guizhou Medical University;Center for Microbial and Biochemical Engineering,Guizhou Medical University;

摘要(Abstract):

建立UPLC-MS/MS研究在正常大鼠和肠道菌群失调大鼠体内,聚乙二醇400(PEG400)对黄芩苷、黄芩素在正常大鼠和肠道菌群失调大鼠体内的药代动力学的影响。以染料木素为内标,血浆样品经乙酸乙酯沉淀蛋白,UPLC-MS/MS测定,方法经专属性、线性范围、准确度、精密度、稳定性等确证适合用于血浆中黄芩苷的测定。采用盐酸林可霉素(5 g·kg-1·d-1)造模1周,诱导菌群失调大鼠模型。正常大鼠和肠道菌群失调大鼠分别灌胃黄芩苷、黄芩苷+PEG400、黄芩素和黄芩素+PEG400后不同时间点取血浆,UPLC-MS/MS测定给药后血浆中黄芩苷的浓度,采用DAS 3. 2. 2软件计算药动学参数,绘制血药浓度-时间曲线图。结果显示盐酸林可霉素诱导的菌群失调大鼠粪便中β-葡萄糖醛酸苷酶活性和菌落数显著降低。肠道菌群失调大鼠黄芩苷+PEG400组的Cmax和AUC0-t显著低于正常大鼠黄芩苷+PEG400组。菌群失调大鼠黄芩苷组和黄芩苷+PEG400组的Cmax和AUC0-t无显著性差异。正常大鼠黄芩苷组的Cmax和AUC0-t显著高于肠道菌群失调大鼠黄芩苷组和黄芩苷+PEG400组。正常大鼠黄芩素+PEG400组的Cmax和AUC0-t与黄芩素组无显著性差异。菌群失调大鼠黄芩素组的Cmax和AUC0-t低于正常组但显著高于黄芩素+PEG400组。结果表明,PEG400能够增加正常大鼠体内黄芩苷的吸收,菌群失调大鼠体内则无效,不影响黄芩素在大鼠体内的吸收。
The study aimed to establish an UPLC-MS/MS method for the determination of baicalin in rat plasma,in order to study the effect of PEG400 on pharmacokinetics of baicalin and baicalein in normal and gut microbiotadysbiosis rats. Plasma was precipitated with ethyl acetate and determined by UPLC-MS/MS method,with genistein as an internal standard. In terms of specificity,linearity,range,accuracy,precision and stability,the method was suitable for the determination of baicalin in plasma. The gut microbiotadysbiosis rat model was induced through the oral administration with lincomycin hydrochloride(5 g·kg-1·d-1) for one week. Samples of plasma of rats were obtained at different time points,after the rats were administrated with baicalin,baicalin and PEG400. Baicalin in rats were detected by UPLC-MS/MS method,and pharmacokinetic parameters were calculated by DAS 3. 2. 2 software. The results showed that the β-glucosidase activity and the number of colonies in the feces of gut microbiotadysbiosis rats induced by lincomycin hydrochloride were significantly reduced. The Cmaxand AUC0-tof the baicalinand PEG400 group in the intestinal flora were significantly lower than those in the normal rat baicalin and PEG400 group. There was no significant difference in Cmaxand AUC0-tbetween the baicalin group and the baicalin+PEG400 group of gut microbiotadysbiosis rats. The Cmaxand AUC0-tof the normal rats baicalin group were significantly higher than those of the gut microbiotadysbiosis rats baicalin group and the baicalin + PEG400 group. There was no significant difference in Cmaxand AUC0-tbetween the normal rat baicalein and PEG400 group and the baicalein group. The Cmaxand AUC0-tof the baicalein group in the gut microbiotadysbiosis rats were lower than those in the normal baicalein group,but significantly higher than those in the baicalein and PEG400 group. PEG400 could increase the absorption of baicalin in normal rats,but is ineffective in gut microbiotadysbiosis rats,with no impact on the absorption of baicalein in rats.

关键词(KeyWords): 黄芩苷;黄芩素;PEG400;菌群失调;药代动力学
baicalin;baicalien;PEG400;gut microbiotadysbiosis;pharmacokinetics

Abstract:

Keywords:

基金项目(Foundation): 贵州省普通高等学校工程研究中心课题项目(黔教合KY字[2015]

作者(Author): 顾腾;张硕;张敏;孟小夏;高秀丽;
GU Teng;ZHANG Shuo;ZHANG Min;MENG Xiao-xia;GAO Xiu-li;Pharmaceutical College,Guizhou Medical University;State Key Laboratory of Functions and Appliactions of Medical Plants,Guizhou Medical University;Center for Microbial and Biochemical Engineering,Guizhou Medical University;

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