[关键词]
[摘要]
目的 研究组合药物（小檗碱＋黄芩苷＋栀子苷）及黄连解毒汤复方对小檗碱在大鼠脑组织药动学的影响。方法 SD大鼠，分为小檗碱（247.39 mg/kg）组、组合药物（小檗碱、黄芩苷、栀子苷，247.39、130.11、113.01 mg/kg）组、黄连解毒汤（3.92 g/kg，小檗碱247.39 mg/kg）组，各组分别ig相应剂量的药物，分别于给药后0.083、0.25、0.5、1、2、4、6、8、12、24 h各取6只大鼠，处死取脑组织，UPLC-MS法测定小檗碱在脑组织中的质量浓度。计算各组中小檗碱药动学参数。结果 与小檗碱组达峰浓度（Cmax 108.01 ng/g）相比，组合药物组小檗碱的Cmax（368.59 ng/g）显著增加，明显高于黄连解毒汤原方给药中小檗碱的Cmax（31.97 ng/g）；组合药物组的AUC0~∞（3 236.60 min·ng/g）远大于小檗碱组的AUC0~∞（2 701.37 min·ng/g）和黄连解毒汤组的AUC0~∞（420.34 min·ng/g）。结论 与小檗碱组相比，组合药物能促进小檗碱进入脑组织，而黄连解毒汤复方抑制小檗碱进入脑组织。
[Key word]
[Abstract]
Objective To investigate the variation in pharmacokinetics of berberine in the brain tissue of rats under the conditions of compound compatibility with geniposide and baicalin or the primary formula HuanglianJiedu Decoction (HJD). Methods The rats were divided into three groups including berberine group (247.39 mg/kg), compound combination group (berberine, geniposide, and baicalin of 247.39, 130.11, and 113.01 mg/kg) and HJD group (HJD 3.92 g/kg and berberine 247.39 mg/kg). After ig administration of those compounds or formula, the brain tissues of rats were collected immediately at 0.083, 0.25, 0.5, 1, 2, 4, 6, 8, 12, and 24 h respectively. The brain tissue was taken from the six rats in each group. A sensitive UPLC-MS method was developed for determining the concentration of berberine in the brain tissue of rats. The concentration-time curve was plotted and the pharmacokinetic parameters of rats in each group were calculated by DAS 2.0 software. Results These results showed that the Cmax (368.59 ng/g) of berberine in rats with compound combination was increased compared with those with berberine alone (Cmax 108.01 ng/g), which is pronouncedly larger than the Cmax (31.97 ng/g) of berberine in the HJD group. Meanwhile, the AUC0—∞ of berberine in the compound combination group was 3 236.60 min·ng/g which was much greater than the AUC0—∞ in rat brain with berberine (2 701.37 min·ng/g) or HJD (420.34 min·ng/g). Conclusion The combination of geniposide and baicalin could promote the concentration of berberine, while the primary formula HJD could decrease the distribution of berberine in the brain tissue of rats.
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[基金项目]
国家自然科学基金资助项目（81303230，81072749）；江苏省科技厅自然科学基金项目（BK2012855）；江苏省六大人才高峰项目（2014-YY-014）；江苏省中药资源产业化过程协同创新中心重点项目（ZDXM-1-6）；江苏省高校优势学科建设工程资助项目；南京中医药大学校级创新团队资助
