黄连解毒汤中小檗碱及其他成分模拟组合在脑缺血大鼠体内药动学比较研究

Comparative study on in vivo pharmacokinetics of simulated combination of berberine and other ingredients in Huanglian Jiedu Decoction in rats with cerebral ischemia

目的比较基于黄连解毒汤原方比例的4种不同模拟组合中主成分小檗碱在脑缺血模型大鼠体内的药动学变化过程。方法大鼠按体质量分为模型组和假手术组,模型组以线栓法复制大鼠脑缺血模型。每组又分为4个亚组,分别为小檗碱(247.4 mg/kg)组、小檗碱(247.4 mg/kg)+黄芩苷(190.7 mg/kg)组、小檗碱(247.4 mg/kg)+栀子苷(149.5 mg/kg)组、小檗碱(247.4 mg/kg)+栀子苷(149.5 mg/kg)+黄芩苷(190.7 mg/kg)组。各组分别于ig给药后0.083、0.25、0.5、1、2、3、4、6、8、10、12、24、48、72 h眼眶取血,HPLC法测定小檗碱在大鼠血浆中的浓度变化,绘制药-时曲线,DAS2.0计算药动学参数。结果根据统计矩参数,模型组和假手术组小檗碱的吸收顺序均为小檗碱+栀子苷组>小檗碱+栀子苷+黄芩苷组>小檗碱组>小檗碱+黄芩苷组。结论针对脑缺血模型,黄连解毒汤中的栀子苷可促进小檗碱的吸收,黄芩苷则对小檗碱的吸收有一定的抑制作用,而三者组合给药后栀子苷可以降低黄芩苷对小檗碱吸收的抑制作用。

Objective To compare the pharmacokinetic changing process of the main component berberine in four different simulated combinations based on the proportion of Huanglian Jiedu Decoction （HJD） in rats with cerebral ischemia. Methods According to body weight the rats were divided into model and Sham groups, and the middle cerebral artery occlusion （MCAO） was reproduced by suture method to make rats with cerebral ischemia in the model group. Each group was divided into four sub-groups： berberine （247.4 mg/kg）, berberine （247.4 mg/kg） ＋ baicalin （190.7 mg/kg）, berberine （247.4 mg/kg） ＋ geniposide （149.5 mg/kg）, and berberine （247.4 mg/kg） ＋ geniposide （149.5 mg/kg） ＋ baicalin （190.7 mg/kg） groups. After ig administration, orbital blood was collected in 0.083, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, and 72 h, respectively. HPLC method was used for the determination of berberine concentration change in rat plasma. The concentration-time curve was plotted and the pharmacokinetic parameters were calculated by DAS 2.0. Results According to the statistical parameters, the absorbed order of berberine in the model and Sham groups was as follows： berberine ＋ geniposide 〉 berberine ＋ geniposide ＋ baicalin 〉 berberine 〉 berberine ＋ baicalin. Conclusion For MCAO rats, geniposide in HJD could promote the absorption of berberine, and baicalin could inhibit the absorption ofberberine, but the combination of the three could alleviate the inhibition of berberine absorption by baicalin.