戊己丸配伍对代表成分体内药代动力学和组织分布的影响  

Effect of Compatibility of Wujiwan on Pharmacokinetics and Tissue Distribution ofRepresentative Components

作　　者：董宇[1] 陈颖[2] 巩仔鹏[3] 杨庆[2] 翁小刚[2] 王娅杰[2] 朱晓新[2] 张辰浩[4] DONG Yu;CHEN Ying;GONG Zipeng;YANG Qing;WENG Xiaogang;WANG Yajie;ZHU Xiaoxin;ZHANG Chenhao(Guang′anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Guizhou Provincial Key Laboratory of Pharmaceutics,Guizhou Medical University,Guizhou 550004,China;Wangjing Hospital,China Academy of Chinese Medical Sciences,Beijing 100102,China)

机构地区：[1]中国中医科学院广安门医院,北京100053 [2]中国中医科学院中药研究所,北京100700 [3]贵州医科大学贵州省药物制剂重点实验室,贵阳550004 [4]中国中医科学院望京医院,北京100102

出　　处：《中国实验方剂学杂志》2024年第3期105-113,共9页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：中国中医科学院科技创新工程重大攻关项目(CI2021A04908,CI2021A04905);国家自然科学基金项目(81001684,82074103)。

摘　　要：目的:研究戊己丸中5个代表成分血浆药代动力学及组织分布的情况,从戊己丸在配伍前后体内代谢和组织分布的差异变化说明方剂配伍的特点。方法:将260只健康雄性SD大鼠分为戊己丸组(62.96 g·L^(-1))、黄连组(38.4 g·L^(-1))、制吴茱萸组(5.88 g·L^(-1))、炒白芍组(18.68 g·L^(-1)),每组65只,按临床饮片剂量折算成提取物剂量给药,给药后每组按药代动力学设定时间取血浆、肝、小肠和脑。采用超高效液相色谱-三重四极杆串联质谱法建立戊己丸中5个代表成分小檗碱(Ber)、巴马汀(Pal)、吴茱萸碱(Evo)、吴茱萸次碱(Rut)和芍药苷(Pae)在血浆、肝、小肠和脑中定量分析方法,血浆样品采用蛋白沉淀法、组织样品采用蛋白沉淀加液-液萃取法进行前处理,对各组给药前、给药后不同时间点血浆和组织样品进行代表成分的检测。采用非房室模型计算各成分药代动力学参数,并对各组药代参数进行比较。结果:戊己丸组药代动力学结果显示,5种代表成分药-时曲线下面积(AUC_(0-t))大小排序如下:Ber和Pal为小肠>肝>血浆;Evo和Rut为肝>小肠>血浆;Pae为小肠>血浆,未在肝脏中检出;脑中除Ber外未检测到其他成分;与血浆及其他组织比较,戊己丸组肝脏中Ber、Pal、Evo、Rut的药峰浓度(C_(max))均为最高且达峰时间(t_(max))均为最低。在血浆中,与制吴茱萸组比较,戊己丸组中Evo和Rut的AUC_(0-t)和C_(max)均增加,与炒白芍组比较,戊己丸组中Pae的t_(max)升高、C_(max)降低;在肝脏中,与各单味药组比较,戊己丸组中除Pae外各代表成分的C_(max)均升高,Pal的AUC_(0-t)降低,Evo和Rut的AUC_(0-t)升高;在小肠中,与各单味药组比较,戊己丸组中各代表成分的半衰期(t1/2)升高、t_(max)降低,除Pal外各代表成分Cmax降低,Ber、Pal的AUC0-t升高,Evo和Rut的AUC_(0-t)则降低。结论:小肠作为戊己丸的效应器官分布最多,其次为肝脏;戊己丸在配伍前后各代�Objective:To study the plasma pharmacokinetics and tissue distribution of five representative components in Wujiwan,and to illustrate the difference of metabolism and tissue distribution before and after compatibility.Method:Healthy male SD rats were divided into four groups,including Wujiwan group(A group,62.96 g·L^(-1)),Coptidis Rhizoma group(B group,38.4 g·L^(-1)),processed Euodiae Fructus group(C group,5.88 g·L^(-1))and fried Paeoniae Radix Alba group(D group,18.68 g·L^(-1)),with 65 rats in each group,and were administered the drugs according to the clinical dose of decoction pieces converted into the dose of the extracts.Then plasma,liver,small intestine and brain were taken at pharmacokinetic set time in each group after administration.Ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry was developed for the quantitative analysis of five representative components[berberine(Ber),palmatine(Pal),evodiamine(Evo),rutecarpine(Rut)and paeoniflorin(Pae)]in Wujiwan,their concentrations in plasma,liver,small intestine and brain were detected at different time,plasma samples were processed by protein precipitation,and tissue samples were pretreated by protein precipitation plus liquid-liquid extraction.Non-atrioventricular model was used to calculate the pharmacokinetic parameters of each component,and the parameters of each group were compared.Result:Pharmacokinetic results of A group showed that area under the curve(AUC_(0-t))of the five representative components were ranked as follows:Ber and Pal were small intestine>liver>blood,Evo and Rut were liver>small intestine>plasma,Pae was small intestine>plasma,which was not detected in the liver,no other components were detected in brain except for Ber.In comparison with plasma and other tissues,peak concentration(C_(max))of Ber,Pal,Evo,and Rut were the highest and time to peak(t_(max))were the lowest in the liver of A group.In plasma,the AUC_(0-t) and C_(max) of Evo and Rut were increased in A group compared with C group,t_(max) o

关 键 词：戊己丸 方剂配伍 药代动力学 组织分布 黄连 吴茱萸 白芍 

分 类 号：R22[医药卫生—中医基础理论] R28[医药卫生—中医学] R969.1[理学—分析化学] O657[理学—化学]