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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。
OBJECTIVE: To study the relationship between dosage, time and method of tolerance to rhubarb in mice and the relationship between tolerance to rhubarb and intestinal tract free anthraquinone, To provide a basis for the clinical rational use of rhubarb. Methods: ED95 of Rhubarb causing mice diarrhea was low dose and ED95 was twice as high dose. The mice were divided into blank group, low-dose rhubarb group, high-dose rhubarb group, low-dose rhubarb group, rhubarb High dose of the second day of the administration group, daily and every other day gavage, were administered 10 times. The water content of feces, the number of excrement and the carbon excretion time after stopping were observed. HPLC and HPLC were used to detect the effect of high dose rhubarb on day 1 and day 10 and high dose rhubarb on the other day The relative ratio of fecal-bound anthraquinone and free anthraquinone peak areas after 10 administrations. Results: In the same dose of rhubarb administered every other day, the effect of diarrhea was the lightest and easy to recover. The relative ratio of fecal-bound and free anthraquinone peak area was the lowest in the rhubarb administration group after the tenth administration The relative ratio of fecal bound and free anthraquinone in the high-dose daily group after the tenth administration. CONCLUSION: The mice are tolerant to rhubarb and its dose, the administration time and administration method are related to the administration of anthraquinone in the intestinal tract, while the administration of larger doses of rhubarb may reduce the small Secondary to secondary purgative effect tolerance.