舒肝宁注射液及其方中黄芩提取物在大鼠肝微粒体、尿液、粪便、胆汁中的代谢比较研究  

Comparative study on metabolism of Scutellariae Radix extract in Shuganning Injection and prescription in rat liver microsomes,bile,urine and feces

作　　者：何峰 周杨 彭玥 郑林[2] 王玲 黄勇 迟明艳[1,3] HE Feng;ZHOU Yang;PENG Yue;ZHENG Lin;WANG Ling;HUANG Yong;CHI Ming-yan(School of Pharmaceutical Sciences,Guizhou Medical University,Guiyang 550004,China;Guizhou Provincial Key Laboratory of Pharmaceutics,State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University,Guiyang 550004,China;Engineering Research Center for Development and Application of Ethnic Medicine and Traditional Chinese Medicine,Guizhou Medical University,Guiyang 550004,China)

机构地区：[1]贵州医科大学药学院,贵州贵阳550004 [2]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,贵州贵阳550004 [3]贵州医科大学民族药与中药开发应用教育部工程研究中心,贵州贵阳550004

出　　处：《中国中药杂志》2024年第23期6500-6511,共12页China Journal of Chinese Materia Medica

基　　金：贵州省科技计划项目(黔科合成果[2022]013,黔科合支撑[2023]一般158,黔科合平台人才-CXTD[2023]019,黔科合中引地[2023]006);贵州省高层次创新型人才项目(黔科合平台人才-GCC[2022]031-1)。

摘　　要：比较舒肝宁注射液和黄芩提取物中黄芩苷及其类似物的代谢差异。12只SD大鼠随机分为舒肝宁注射液组和黄芩提取物组,每组6只,将肝微粒体与药物共孵育后收集样品,采用超高效液相色谱-四极杆-静电场轨道阱高分辨质谱法(UPLC-Q-Exactive Orbitrap-MS)分析肝微粒体中各组药物的原型成分与代谢产物。另取12只SD大鼠随机分为舒肝宁注射液组和黄芩提取物组,每组6只,尾静脉给予4.2 mL·kg^(-1)的舒肝宁注射液或黄芩提取物,给药48 h后收集大鼠尿液、粪便和胆汁,采用UPLC-Q-Exactive Orbitrap-MS分析各生物样品中的原型及代谢产物。结果表明,舒肝宁注射液及黄芩提取物在肝微粒体中共鉴定出原型成分5个,代谢产物8个;在大鼠尿液、粪便和胆汁中均鉴定出5个原型成分,其中,在尿液中鉴定了15个代谢物,粪便中检测到9个代谢物,在胆汁中鉴定了12个代谢物。比较二者黄芩苷在代谢途径及代谢物数量上的差异,发现二者在肝微粒体、尿液、胆汁和粪便中葡萄糖醛酸化为黄芩苷和黄芩素的主要代谢途径,且存在部分甲基化产物及葡萄糖结合产物。舒肝宁注射液复方与黄芩提取物中,黄芩苷在尿样中代谢产物的数量和种类存在差异,表明二者在代谢上存在差异,说明中药成方中其余成分的存在会导致体内主要成分代谢产物发生变化。To compare the differences of baicalin and its analogues metabolism between Shuganning Injection and single herb extract of Scutellariae Radix.An UPLC-Q-Exactive Orbitrap-MS qualitative analysis method for the prototypes and metabolites of Shuganning Injection or Scutellariae Radix extract in rat liver microsomes,bile,urine and feces was established.The rat liver microsomes were divided into a Shuganning Injection group and Scutellariae Radix extract group,with 6 rats in each group.The liver microsomes were incubated with the drugs and the samples were collected.UPLC-QExactive Orbitrap-MS was used to analyze the prototype components and metabolites of each group of drugs in liver microsomes. In addition, the rats were divided into a Shuganning Injection group and Scutellariae Radix extract group, with 6rats in each group. Rats were intravenous administrated 4.2 mL·kg^(-1) of Shuganning Injection or Scutellariae Radix extract.After 48 hours, the rat urine, feces and bile were collected, and UPLC-Q-Exactive Orbitrap-MS was used to analyze theprototype and metabolites in each biological sample, and the differences in baicalin metabolites in single and compoundformulas were compared. There were differences in the number of metabolites of baicalin in liver micros omes, urine, fecesand bile samples between Shuganning Injection and Scutellariae Radix extract. The results showed that the metabolites ofbaicalin or baicalein were mainly glucuronic acid conjugates, and there were also a small amount of methylation and glucosebinding products. There are differences in metabolites between single prescription and compound prescription, indicating thatthe change of compatibility of traditional Chinese medicine compound prescription will directly lead to the change ofmetabolites in vivo. There were 5 prototype components and 8 liver microsome metabolites in Shuganning Injection andScutellariae Radix extract in liver incubation solution. A total of 5 prototype components were identified in rats. Among them,15 metabolites were id

关 键 词：舒肝宁注射液 茵陈蒿汤 黄芩提取物 UPLC-Q-Exactive Orbitrap-MS 肝微粒体 尿液 粪便 胆汁 

分 类 号：R285.5[医药卫生—中药学]