黄连生物碱在大鼠体内的代谢转化及分布

目的:测定黄连生物碱在大鼠体内的药代动力学、组织分布,及药根碱、黄连碱、巴马汀、小檗碱4种生物碱在大鼠体内的转化。方法:大鼠分别灌胃黄连总碱、小檗碱,采用反相高效液相色谱法测定大鼠的血浆、组织、胃肠道中黄连4种生物碱的含量。结果:小檗碱在大鼠体内的血药浓度出现2个峰值,达峰时间分别2,5h,其中血药浓度分别为Cmax3.7,2.8mg.L-1;小檗碱在大鼠血液中可以转化为药根碱;给大鼠灌胃黄连总生物碱后,小檗碱在大鼠胃中的浓度单调下降,而黄连碱、巴马汀和药根碱逐渐增加,表明在大鼠的胃中小檗碱可转化为药根碱;小檗碱和巴马汀主要分布在动物的肺部,其次分布在肝脏中,而药根碱和黄连碱主要分布在动物的肝脏中,其次分布在肺部。结论:小檗碱可以转化为药根碱,根据胃肠道推进实验部分解释了小檗碱在血液中出现2次峰值的原因。

Metabolism,transformation and distribution of Coptis chinensis total alkaloids in rat

Objective : To determine the pharmacokinetics, distribution and mutual transformation of the total alkaloids, jatrorrhizine, coptisine, berberine and palmatine from Coptis chinensis in rats . Method : After the total alkaloids and berberine were fed into rats, their contents in plasma, tissues and gastrointestinal tract were determined by reversed-phase HPLC. Result : The peak times of berberine in blood were 2.0 h (C_max 3.7 mg·L^-1)and 5.0 h (C_max 2.8 mg·L^-1), respectively. Berberine in rat blood can be transformed into jatrorrhizine. After the rats were fed with the total alkaloids by gavage, the content of berberine was decreased monotonously, while coptisine, palmatine and jatrorrhizine contents were increased gradually in the stomach, it speculated that berberine may be transformed into jatrorrhizine in the stomach. Animal experiments showed that berberine and palmatine were mainly distributed in the lungs of animals, followed by the distribution in the liver, while jatrorrhizine and coptisine was mainly in the liver, then in the lungs. Conclusion : Berberine could transform into jatrorrhizine. The mechanism on the appearance of two maximum blood concentration of berberine in blood could be explained with the propulsion of the gastrointestinal tract partly.