脾虚证大鼠甘草甜素药物动力学特征与胃肠动力的关系研究

STUDY ON RELATIONSHIP BETWEEN PHARMACOKINETICS CHARACTERISTICS OF GLYCYRRHIZIN AND GASTROINTESTINAL MOTIVITY IN RAT MODEL OF SPLEEN DEFICIENCY SYNDROME

目的 :探讨脾虚证大鼠甘草甜素 (GL)的药物动力学 (PK)特征 ,并从胃排空、脑 肠肽两方面探讨其机制。方法 :利血平作用于大鼠 14d ,复制实验性脾虚模型 (C组 ) ;用四君子汤 (A组 )和六味地黄汤 (B组 )治疗以反证 ;用高效液相色谱 (HPLC)法测定大鼠体内GL的血药浓度 ;用同位素检测其胃液体排空功能 ;用放射免疫分析法 (RIA)分析下丘脑和血浆中胃动素 (MOT)、胆囊收缩素 (CCK)及生长抑素 (SS)的浓度。结果 :GL在体内为二室房室PK模型。与正常对照组 (D组 )比较 ,C组大鼠药物动力学相关参数降低 ;胃排空率下降 ,MOT和SS在血浆及下丘脑的水平下降 ,而CCK则上升 ;A组上述各值恢复正常 ,与D组比较无统计学差异 (P >0 .0 5) ;B组与A组比较仍有显著差异 (P <0 .0 5,P <0 .0 1)。结论 :脾虚大鼠胃排空、脑 肠肽浓度的异常 。

Objective:To explore the pharmacokinetics characteristics of glycyrrhizin in rat model of spleen deficiency syndrome(RMSDS) and its mechanism in gastric emptying and brain gut peptide.Method:①RMSDS C group was established by intramuscular injection of reserpine for 14 days and was confirmed by Sijunzi decoction(A group)and Liuwei Dihuang decoction( B group);②The blood drug concentration of glycyrrhizin was determined by HPLC;③30min gastric liquid emptying rate,the plasma and hypothalamus levels of motilin(MOT),cholecystokinin(CCK) and somatostatin(SS) were measured by radioistopic technique,chronically implanted electrodes and RIA,respectively.Result:The atrioventricular model of GL in rats belonged to the open two ventricular.Compared with normal rats(D group):①The related pharmacokinetics parameters of GL in C group were decreased;②the gastric liquid emptying rate of RMSDS was decreased;③the hypothalamus and plasma levels of MOT and SS reduced,both hypothalamus tissues and plasma had higher levels of CCK than those of controls:④There were no significant disorders in A group.Conclusion:The disorders of gastric liquid emptying and brain gut peptide may be one of the important Mechanism of the different pharmacokinetics characteristics of glycyrrhizin in rat model of spleen deficiency syndrome.