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目的 :探讨脾虚证甘草甜素 (GL)的药物动力学 (PK)特征及其在胃肠机械运动方面的机制。方法 :利血平作用于大鼠 7天和 14天 ,制成实验性脾虚短期 (A组 )和长期 (B组 )模型 ;用四君子汤和六味地黄汤反证 ;用高效液相色谱 (HPLC)法测定大鼠体内GL的血药浓度 ;用高灵敏度传感器记录胃和十二指肠运动波。结果 :与正常对照组 (E组 )比较 :①A组大鼠GL体内为一室房室PK模型 ,其它组均为二室房室模型 ;A组和B组大鼠AUC(16 346 9.8和 950 5.18vs 2 13540 .53,μg .min .mL- 1)、Cmax(872 .2 2和 16 2 .32vs2 12 2 .0 9,μg/mL)和T1/2 ka(16 .39和 2 .86vs 4 7.4 6 ,min)降低 ,且B组较A组明显 ;B组大鼠K12 (0 .0 4vs 0 .0 0 0 0 4 ,min- 1)增大 ,β(0 .0 0 7vs 0 .0 2 ,min- 1)减小。②A组大鼠十二指肠运动增强 ,B组大鼠则运动功能减弱 ,两组的胃运动均减弱 ,且B组较A组更弱。③经四君子汤预防性治疗的大鼠 (C组 )胃肠运动和GL的PK参数与E组比较无显著差异 ,但经六味地黄汤治疗的大鼠 (D组 )各值与E组比较存在显著差异 ,而与B组大鼠无显著差异。结论 :脾虚大鼠对经口服GL后的吸收、转运和消除均存在异常 ;血药浓度和生物利用度降低 ,且脾虚程度越重 ,GL的有效吸收越低 ;胃运动功能减弱 ,可能是脾虚GL的有效吸收降
Objective: To investigate the pharmacokinetic (PK) characteristics of spleen deficiency glycyrrhizin (GL) and its mechanism in gastrointestinal mechanical movement. METHODS: Reserpine was administered to rats for 7 days and 14 days, and a model of experimental spleen deficiency in short-term (group A) and long-term (group B) rats was established; reversed with Sijunzi Decoction and Liuwei Dihuang Decoction; high-performance liquid chromatography (HPLC) was used. The plasma concentration of GL in rats was determined by the method; the high-sensitivity sensor was used to record the motion waves of the stomach and duodenum. RESULTS: Compared with the normal control group (E group), the GL model of rat GL in group 1A was a one-compartmental atrioventricular PK model, and the other groups all had a two-compartment atrioventricular model; rats A and B group AUC (16 346 9.8 and 950). 5.18 vs 2 13540 .53, μg .min .mL- 1), Cmax (872.22 and 16 2 .32 vs2 12 2 .0 9, μg/mL) and T1/2 ka (16 .39 and 2.86 vs. 4 7.4 6 ,min) decreased, and B group was more obvious than group A; group B rats K12 (0.04vs 0.040, min-1) increased, β (0. 0 0 7vs 0. 0 2 ,min - 1) decrease. The duodenum movement in group 2A was increased, while the motor function was decreased in group B. Gastric exercise was weakened in both groups, and group B was weaker than group A. 3There was no significant difference in gastrointestinal motility and PK parameters of GL between the rats treated with Sijunzi Decoction and group E (P>0.05). However, the rats treated with Liuwei Dihuang Decoction (group D) had different values compared with E group. Significant difference, but no significant difference with group B rats. Conclusion: Absorption, translocation and elimination of spleen deficiency rats after oral administration of GL are all abnormal. Blood concentration and bioavailability are decreased. The more severe the spleen deficiency is, the lower the effective absorption of GL is. The gastric motor function may be spleen deficiency. GL’s effective absorption drop