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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。
OBJECTIVE: To compare the differences of hypaconitine concentrations in the serum of hypoglycemic mice and normal mice, and to analyze the difference of metabolic environment in different organs, and to prove that the occurrence of drug toxicity is related to the metabolic environment of the body at the metabolic level. Methods: The model of asthenia cold mice was duplicated, and the aconite decoction was administered continuously for 14 days. The hypoxemic acid concentrations in the serum of mice on day 1,7 and 14 were detected by HPLC. The survival of mice was also observed rate. Results: The aconite decoction played a regulatory role on the body metabolism of mice in the Deficiency state. After 14 days of administration, the plasma concentration of Fuzi decoction restored or approached the normal level. The Aconitum decoction disturbed the metabolism of the mice in the normal group, The blood concentration of the drug on day 7 and day 14 were higher than that on the first day. Within the dosing period of 14 d, the change range of plasma concentration of asthenic group was less than that of the normal group. On the 7th day and the 14th day after the aconite decoction was administered, the survival rate of mice in the Deficiency state was significantly higher than that in the normal group. CONCLUSION: The difference of blood concentration in normal and asthenic mice suggests that there is a difference in the metabolic environment between normal and asthenic mice, and the metabolic environment is changed during the administration of aconite decoction. The experimental results to some extent that the aconite clinical toxicity of different doses and the body’s metabolic environment is different.