半夏泻心汤及其苦降药组促进胃肠动力的PK-PD研究  

PK-PD Study on Banxia Xiexin Decoction and its bitter medicine group on effect of promoting gastrointestinal motility

作　　者：罗太敏 李晋奇[2] 杨戈 张德 童荣生[2] 

机构地区：[1]天府新区人民医院,四川成都610213 [2]四川省医学科学院.四川省人民医院,四川成都610072

出　　处：《药物评价研究》2015年第6期622-628,共7页Drug Evaluation Research

摘　　要：目的探讨半夏泻心汤促进胃肠动力的物质基础、作用机制和配伍特点。方法将实验分为半夏泻心汤组及苦降药组,两组大鼠分别ig 给予两组药物水提醇沉液,于给药前(0 h)及给药后0.083、0.167、0.25、0.333、0.5、0.75、1、1.5、2、3、4、6、9、24 h 股静脉采血,ELISA 法测Cajal 间质细胞(ICC)中KIT 蛋白、Ca2+及ATP 酶的水平,同时采用液质联用(HPLC-MS)法检测血清中黄芩苷、黄芩素、小檗碱、巴马汀的浓度,采用Winnonlin 软件进行药动学(PK)- 药效学(PD)结合模型合。结果半夏泻心汤及其苦降药组均能下调 ICC 中Ca2+浓度及上调ICC 中ATP 酶的水平;且对ICC 内KIT 蛋白水平无显著影响。半夏泻心汤及其苦降药组降低Ca2+浓度的效应中巴马汀以有滞后时间三房室-Sigmoid ImaxPK-PD模型连接,小檗碱、黄芩素以有滞后时间二房室-Sigmoid Imax PK-PD 模型连接。半夏泻心汤及其苦降药组上调ATP 酶的效应中巴马汀以有滞后时间三房室-Sigmoid Emax PK-PD 模型连接,小檗碱、黄芩素以有滞后时间二房室-Sigmoid Emax PK-PD模型连接。结论半夏泻心汤及其苦降药组促进胃肠动力的作用可能与其降低ICC 内Ca2+浓度、上调细胞ATP 酶水平有关。ICC 内Ca2+浓度的降低、ATP 酶水平的上调可能与半夏泻心汤及其苦降药组中巴马汀、小檗碱、黄芩素有关。半夏泻心汤在PK 和PD 方面均优于苦降药组,体现出全方的配伍优势。Objective To investigate the material basis, mechanism, and compatibility characteristics of Banxia Xiexin Decoction(BXD) in promoting the gastrointestinal motility. Methods The rats were divided into BXD group and bitter medicine group. Blood samples were collected before administration (0 h) and 0.083, 0.167, 0.25, 0.333, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 9, 24 h after administration by venous blood collection. ELISA method was used to detect the changes of KIT protein content, Ca2+ concentration, and ATP enzyme level at different time points in BXD group and bitter medicine group. HPLC-MS method was established for simultaneous determination of baicalin, baicalein, berberine, and palmatine in rat plasma. Winnonlin software was used to fit PK-PD model. Results In BXD and bitter medicine groups, the Ca2+ concentration was decreased and the ATP enzyme level was increased in ICC. BXD and bitter medicine containing serum had no significant effect on KIT protein. By fitting the berberine, baicalin, and palmatine of BXD group with Ca2+ concentration, to identify palmatine was connected to effect room with lag time three compartment-Sigmoid Imax PK-PD model. Berberine, baicalin were connected with lag time two compartment-Sigmoid Imax PK-PD model. By fitting the berberine, baicalin, palmatine of BXD group with ATP enzyme, to identify palmatine was connected to effect room with lag time three compartment-Sigmoid Emax PK-PD model. Berberine, baicalin were connected with lag time two compartment- Sigmoid Emax PK-PD model. Conclusion BXD and bitter medicine group in promoting gastrointestinal function may be related to the reduction of Ca2+concentration and upregulation of ATP enzyme in ICC. The decreasing of Ca2+ concentration and increasing of ATP enzyme level may be related to berberine, baicalin, and palmatine in BXD and its bitter medicine. PK and PD in BXD are superior to the bitter medicine group, which shows the advantages of full compatibility.

关 键 词：半夏泻心汤 PK-PD模型 CAJAL间质细胞 KIT蛋白 Ca2+浓度 ATP酶 

分 类 号：R285.5[医药卫生—中药学]