常态及虚寒状态小鼠体内次乌头碱的血药浓度差异研究

目的:对比研究虚寒状态和常态小鼠血清中次乌头碱浓度差异,分析不同机体代谢环境的差异,在代谢层面说明药物毒性发生与机体的代谢环境有关。方法:复制小鼠虚寒状态模型,连续给予附子水煎液14d,用HPLC检测第1,7,14天虚寒状态及常态小鼠血清中次乌头碱的浓度;同时观察小鼠的存活率。结果:附子水煎液对虚寒状态小鼠机体代谢起调节作用,给药14d后,其血药浓度恢复或接近正常组水平;附子水煎液对常态组小鼠的体内代谢环境存在扰动,给药7,14d的血药浓度均比第1天高;在14d的给药周期内,虚寒组血药浓度的变化范围小于正常组。附子水煎液灌胃后第7天及第14天,虚寒状态组小鼠的存活率明显高于常态组小鼠。结论:常态及虚寒状态小鼠血药浓度的差异提示常态和虚寒状态小鼠的代谢环境存在差异,代谢环境在给予附子水煎液的过程中发生改变。实验结果在一定程度上说明附子在临床上产生毒性的剂量不同与机体的代谢环境不同有关。

Difference of hypaconitine concentration in serum between cold-deficiency and normal mice

Objective : To investigate the difference of hypaconitine concentration in serum between normal and cold-deficiency mice after administration of aconite decoction. To analyze how the toxic dose of aconite decoction correlate to the metabolic environment. Method : Prepared cold-deficiency mice model, treated normal and cold-deficiency mice with aconite decoction for 14 days continuously, and then detected hypaconitine concentration in serum by HPLC along with survival ratio of mice on the first, seventh and fourteenth day. Result : After administration of aconite decoction for 14 days, the hypaconitine concentration in serum of cold-deficiency mice is close to that in normal mice. It showed aconite decoction has the ability of regulating metabolism environment, the hypaconitine concentration in serum of normal mice was higher on the seventh and fourteenth day than that on first day. It showed that aconite decoction can disturb metabolism environment of normal mice. It was also been observed that the range of variation of hypaconitine concentration in cold-deficiency mice was minor than that in normal mice during the fourteen days' administration. Conclusion : The difference of serum concentration in normal and cold-deficiency mice showed that there were different metabolic environments in two mice models, and the metabolic environment changed during administration. These results showed that the different toxic doses of aconite decoction were partially due to the different metabolic environments.