小鼠对大黄泻下作用产生耐受性与肠道蒽醌变化关系的量-时-效关系研究

目的:研究小鼠对大黄泻下作用产生耐受性与的给药剂量、时间与方法的关系,以及大黄泻下作用的耐受性与肠道结合型和游离型蒽醌比值变化的关系,为临床合理运用大黄提供依据。方法:以大黄致小鼠泻下作用的ED95为低剂量,2倍ED95为高剂量,将小鼠分为空白组、大黄低剂量组、大黄高剂量组、大黄低剂量隔日给药组、大黄高剂量隔日给药组,每日和隔日灌胃给药,均给药10次。分别观察粪便含水率、粪便粒数、停药后炭末排出时间的变化,并运用高效液相(HPLC)检测大黄高剂量组给药后第1、10日以及大黄高剂量隔日给药组第10次给药后粪便结合蒽醌和游离蒽醌色谱峰面积的相对比值。结果:相同剂量给药以大黄隔日给药发生泻下作用耐受最轻且易恢复;大黄高剂量隔日给药组第10次给药后粪便结合型和游离型蒽醌色谱峰面积相对比值低于每日高剂量组第10次给药后粪便结合型和游离型蒽醌相对比值。结论:小鼠对大黄泻下作用产生耐受性与给药剂量、给药时间和给药方法有关,给药方法对肠道蒽醌变化影响较大,大黄间断较大剂量给药可减少小鼠继发性泻下作用耐受。

Research About Dose -Time -Effect Relation Between Rhubarb Induced Mouse Diarrhoea Tolerance and Intestinal Tract Anthraquinone Dynamic Change

Objective： Research the quantity - time - effect relation of Rhubarb induced mouse diarrhoea tolerance and intestinal tract anthraquinone dynamic change for reasonable useing Rhubarb in clinic. Methods ： Low dose of Rhubarb was decided by its potency of decanta ED95, high dose of Rhubarb was decided by two times of EDge. Mice are divided into blank group, every day low - dose group, every day high - dose group, every other day low - dose group, every other day high - dose group. Intragastric administrated every day and every other day 10 times. Water ratio, stool number, efflux time of Carbo Medicinalis are observed, and high performance liquid chromatogram （HPLC） are used to detect the ratio of yoked anthraquinone and liberated anthraqui- none. Results：At same dose, Rhubarb Intragastric administrated every other day induced mouse costive more slight than other groups ,after 10 times intragastric administration ,every other day high -dose group＇s ratio of yoked anthraquinone and liberated anthraquinone was lower than every day high - dose group＇ s. Conclusion ： Interrupted administration may decrease Rhubarb in- duced diarrhoea tolerance.