异功散中陈皮对脾虚大鼠MTL分泌和人参皂苷Rb1药动学影响及PK-PD相关性分析  

Effect of Pericarpium Citri Reticulatae in Yigong San on MTL secretion and pharmacokinetics of ginsenoside Rb1 in spleen deficiency syndrome rats and correlation analysis of PK-PD

作　　者：段新屹 兰昀羲 沈龙宇 朱昕昀 黄巍[1] DUAN Xin-yi;LAN Yun-xi;SHEN Long-yu;ZHU Xin-yun;HUANG Wei(Chengdu University of Traditional Chinese Medicine,Chengdu,Sichuan 610000,China)

机构地区：[1]成都中医药大学,四川成都610000

出　　处：《时珍国医国药》2024年第7期1781-1786,共6页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金(81860816)。

摘　　要：目的通过比较异功散全方组与异功散去陈皮方组脾虚大鼠体内MTL分泌结果和人参皂苷Rb1药代动力学特征的差异,分析参数PK-PD相关性,探讨行气药能否增效补益剂。方法采用脾虚大鼠灌胃给药异功散全方(Y组)、异功散去陈皮方(Y-C组)、单味陈皮方(C组)及生理盐水(M组),于颈静脉不同时间点取血,运用液质联用方法检测人参皂苷Rb1血浆浓度、ELISA法检测MTL血浆浓度,拟合PK-PD模型。结果2个组药时曲线均呈双峰,Cmax、Tmax均有两个值,Y组两次达峰浓度均明显高于Y-C组(P<0.001),Y-C组第2次吸收量明显多于第1次(P<0.01)。灌胃后16、36h,各给药组大鼠血浆中MTL含量均明显增高(P>0.05),Y组>Y-C组>C组。PD结果为Y组EC_(50)、γ平均值低于Y-C组、Emax平均值高于Y-C组,与PK-PD模型拟合结果基本一致。PK-PD模型拟合结果为Y组Ka1、Ka2、AUC0-t、CL1、CL2、CL3、F、Tlag、EC_(50)、Emax平均值更大;Y-C组Vd1、Vd2、γ、Ke0值更大。结论脾虚大鼠体内人参皂苷Rb1及MTL血药浓度改变与灌胃所用异功散含陈皮有一定相关性。异功散中陈皮发挥增强补益剂补益功效的作用机制之一可能是通过促进异功散中人参皂苷Rb1的吸收增多、吸收速率增快,分布更集中于效应部位,使人参皂苷Rb1与MTL之间亲和力更强,从而导致MTL分泌增多,促进胃肠运动。Objective In order to explore whether Qi-promoting drugs promote the efficacy of tonics,this study analyzed the PK-PD correlation by comparing the difference of MTL secretion results and pharmacokinetic characteristics of ginsenoside Rb1 in spleen deficiency rats between Yigong San group and Yigong San without tangerine peel group.Methods The spleen deficiency syndrome rats were intragastrically administered with Yigong San(Y group),Yigong San without Pericarpium Citri Reticulatae(Y-C group),single Pericarpium Citri Reticulatae(C group)and normal saline(M group),and then blood was taken from jugular vein at different time points.The plasma concentration of ginsenoside Rb1 was detected by liquid chromatography-mass spectrometry,and the plasma concentration of MTL was detected by ELISA.The PK-PD model was fitted.Results The drug-time curves of the two groups showed double peaks,and there were two Cmax and two Tmax in the two groups.The peak concentration of Y group was significantly higher than that of Y-C group(P<0.001),and the second absorption of Y-C group was significantly higher than that of the first time(P<0.01).At 16h and 36h after intragastric administration,the content of MTL in plasma of rats in each administration group was significantly increased(P>0.05),Y group>Y-C group>C group.The results of PD showed that the mean values of EC_(50)andγin Y group were lower than those in Y-C group,and the mean value of Emax was higher than that in Y-C group,which was basically consistent with the fitting of PK-PD model.The fitting results of PK-PD model showed that the average values of Ka1,Ka2,AUC0-t,CL1,CL2,CL3,F,Tlag,EC_(50)and Emax in Y group were larger,and the values of Vd1,Vd2,γand Ke0 in the Y-C group were larger.Conclusion The changes of blood concentration of ginsenoside Rb1 and MTL in spleen deficiency syndrome rats have a certain correlation with the the content of Pericarpium Citri Reticulatae in Yigong San.One of the mechanisms of Pericarpium Citri Reticulatae in Yigong San to enhance the tonic effec

关 键 词：异功散 陈皮 脾虚 人参皂苷RB1 MTL 药动学 药效学 PK-PD结合模型 

分 类 号：R285.5[医药卫生—中药学]