戊己丸中活性成分在正常大鼠和肠易激综合征大鼠体内药代动力学行为的差异性分析  

Difference Analysis of Pharmacokinetic Behavior of Active Ingredients in Wujiwan Between Normal Rats and Rats with Irritable Bowel Syndrome

作　　者：张红[1,2] 陈颖 巩仔鹏[2,3] 董宇[4] 杨紫玉[2] 杨庆 李玉洁[2] 蔡维艳[2] 翁小刚[2] 王娅杰[2] 李琦[2] 臧远龙[1,2] 朱晓新 ZHANG Hong;CHEN Ying;GONG Zi-peng;DONG Yu;YANG Zi-yu;YANG Qing;LI Yu-jie;CAI Wei-yan;WENG Xiao-gang;WANG Ya-jie;LI Qi;ZANG Yuan-long;ZHU Xiao-xin(Anhui University of Chinese Medicine,Hefei 230038,China;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Provincial Key Laboratory of Pharmaceutics in Guizhou Province,State Key Laboratory of Functions and Applications of Medicinal Plants,Engineering Research Center for Development and Application of Ethnic Medicine and Traditional Chinese Medicine,Ministry of Education,School of Pharmaceutical Sciences,Guizhou Medical University,Guiyang 550004,China;Guang'anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China)

机构地区：[1]安徽中医药大学,合肥230038 [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,省部共建药用植物功效与利用国家重点实验室,民族药与中药开发应用教育部工程研究中心,药学院,贵阳550004 [4]中国中医科学院广安门医院,北京100053

出　　处：《中国实验方剂学杂志》2021年第17期124-131,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(82074103);国家“重大新药创制”科技重大专项(2017ZX09101002-002-008,2017ZX09101002-002-002,2017ZX09101002-001-001-3);国家“载人航天工程航天医学实验领域项目”(HYZHXM05003)。

摘　　要：目的:建立超高效液相色谱-串联质谱法(UPLC-MS/MS)测定戊己丸中10个活性成分口服给药后不同时间点的血药浓度,比较其在正常大鼠和慢性内脏高敏感肠易激综合征(CVH-IBS)大鼠体内药代动力学特征的差异。方法:采用乳鼠结肠经皮冠状动脉腔内血管成形术(PTCA)球囊刺激法制备CVH-IBS大鼠模型,灌胃给予戊己丸(给药剂量0.245 g·kg^(-1))后于不同时间点从颈静脉采血,采用UPLC-MS/MS同时检测血浆中10个戊己丸活性成分(盐酸小檗碱、盐酸巴马汀、盐酸黄连碱、盐酸药根碱、表小檗碱、二氢小檗碱、吴茱萸碱、吴茱萸内酯、芍药苷、芍药内酯苷)的血药浓度,计算各成分在正常大鼠和CVH-IBS大鼠体内药代动力学参数的差异。结果:建立的UPLC-MS/MS能够灵敏、准确地检测10个戊己丸活性成分在大鼠体内的血药浓度。与正常组比较,CVH-IBS大鼠体内10个戊己丸活性成分的吸收速率均有一定程度的降低,达峰时间(t_(max))延长,其中盐酸小檗碱和盐酸药根碱的t_(max)分别从54 min和39 min均显著延长至90 min(P<0.05,P<0.01);各成分的药-时曲线下面积(AUC_(0-t))均增加,其中吴茱萸碱和芍药苷差异有统计学意义(P<0.05,P<0.01);10个活性成分的清除率(CL/F)均降低,其中盐酸小檗碱、盐酸巴马汀和吴茱萸碱差异有统计学意义(P<0.05,P<0.01)。结论:戊己丸中活性成分在正常大鼠和CVH-IBS大鼠体内的药代动力学行为存在明显差异,这可能与IBS病理状态下肠道上皮细胞的微结构被破坏和肝脏酶的活性改变有关。Objective:To establish an ultra-performance liquid chromatography-mass spectrometry(UPLC-MS/MS)for determining the plasma concentrations of 10 active ingredients in Wujiwan at different time points after oral administration,and to compare the pharmacokinetic characteristics between normal rats and rats with chronic visceral hypersensitive irritable bowel syndrome(CVH-IBS).Method:CVH-IBS rat model was prepared by the neonatal rat colon percutaneous transluminal coronary angioplasty(PTCA)balloon stimulation method.After intragastric administration of Wujiwan(0.245 g·kg^(-1)),blood was collected from the jugular vein at different time points,and the plasma concentrations of 10 active ingredients(berberine hydrochloride,palmatine hydrochloride,coptisine hydrochloride,jatrorrhizine hydrochloride,epiberberine,dihydroberberine,evodiamine,evodine,paeoniflorin,albiflorin)in Wujiwan was detected simultaneously by UPLC-MS/MS,the pharmacokinetic parameters of each component in normal rats and CVH-IBS rats were calculated.Result:The established UPLC-MS/MS could sensitively and accurately detect the plasma concentrations of 10 active ingredients of Wujiwan in rats.Compared with the normal group,the absorption rates of these 10 active ingredients of Wujiwan in the blood of CVH-IBS rats all decreased to a certain extent,and the peak time(t_(max))was prolonged.Among them,the t_(max)of berberine hydrochloride and jatrorrhizine hydrochloride were significantly prolonged from 54 minute and 39 minute to 90 minute,respectively(P<0.05,P<0.01).Area under the plasma concentration-time curve(AUC_(0-t))of each component increased,and evodiamine and paeoniflorin were significantly different(P<0.05,P<0.01).The clearance rates(CL/F)of these 10 active ingredients were all decreased,among which berberine hydrochloride,palmatine hydrochloride and evodiamine had significant differences(P<0.05,P<0.01).Conclusion:There are significant differences in the pharmacokinetic behavior of the active ingredients in Wujiwan between normal rats and CVH-IBS r

关 键 词：戊己丸 肠易激综合征(IBS) 超高效液相色谱-质谱法(UPLC-MS/MS) 乳鼠结肠球囊刺激法 药代动力学 慢性内脏高敏感性 生物碱 

分 类 号：R22[医药卫生—中医基础理论] R969.1[医药卫生—中医学]