吴茱萸不同组分对胃寒证小鼠急性毒性实验比较研究

摘要

目的：比较吴茱萸水提组分和挥发油对胃寒证小鼠急性毒性的影响，进行证候背景下的吴茱萸急性毒性评价，为中医临床合理应用吴茱萸提供实验依据。方法按持续游泳致体力消耗及灌服冰水的方法，制备小鼠胃寒证模型，采用经典小鼠急性毒性实验方法，进行吴茱萸水提组分和挥发油的小鼠急性毒性实验比较研究，用Bliss法计算半数致死量（LD50），千克体重法计算最大耐受量（MTD），连续观察14天。结果在胃寒证证侯背景下，吴茱萸挥发油的LD50值为2.75 mL·kg-1·d-1，95%的可信限为2.66～2.86 mL·kg-1·d-1；吴茱萸水提组分无法做出LD50，MTD实验结果按含生药量计算为160.0 mL·kg-1·d-1，相当于临床70 kg人每千克体重日用量的2488.8倍。胃寒证小鼠主要的急性毒性症状谱为怠动、腹泻、呼吸抑制，吴茱萸挥发油组小鼠死亡多发生于48h之内。结论吴茱萸不同组分对胃寒证小鼠的急性毒性强度表现为挥发油毒性强度大于吴茱萸水提组分，且均不同程度地小于正常小鼠的急性毒性。%Objective To compare the acute toxicity of water extraction components and volatile oil in Evodia fructus on mice of stomach cold-syndrome, making an observation and evaluation of acute toxicity to Evodia fructus herbs in the syndrome context in order to provide a experimental basis for safe and reasonable medication in clinic. Methods The method of stomach cold-syndrome model in mice was built by continuous swim, leading to exhaustion, and giving ice water mixture in the same time. Comparison of the acute toxicity of water extraction components and volatile oil in Evodia fructus on mice were studied in accordance with classical acute toxicity test methods, and the experimental datas of LD50 and MTD are calculated by the Bliss method, with the continuous administration and observation for 14 days. Results Under the background of stomach cold syndrome, the LD 50 of volatile oil of Evodia fructus is 2.75 mL·kg-1·d-1 and the 95% confidence interval is 2.66~2.86 mL·kg-1·d-1. The water extraction components of Evodia fructus are unable to make LD50, so the result of MTD was 160.0 g·kg-1·d-1 by calculating in accordance with crude drug content, which is equal to 2488.8 times of clinical daily dosage of 70 kg per kilogram of body weight. The main symptoms of acute toxicity in mice of stomach cold-syndrome are ennui energy, diarrhea, respiratory depression, and mice mostly died within 48 h after administration of volatile oil of Evodia fructus. Conclusion Different components of Evodia fructus could cause certain acute toxicity effect on mice with stomach cold-syndrome, and the volatile oil was with the greatest degree of toxicity, followed by the water extracted components.