抑郁模型大鼠灌胃定志小丸提取物后血浆、尿液、粪便、胆汁中主要代谢产物的鉴定  

Identification of the metabolites of Dingzhi Xiaowan extract in depressive rat plasma,urine,feces and bile after intragastric administration

作　　者：许璐[1,2] 刘婉婉[2] 谭潇[2] 王石[2] 穆丽华[2] 董宪喆[2] 王东晓[3] 刘屏[2] 

机构地区：[1]山西中医学院中药学院,山西太原030024 [2]中国人民解放军总医院临床药理研究室,北京100853 [3]中国人民解放军总医院药品保障中心,北京100853

出　　处：《中国中药杂志》2015年第11期2214-2220,共7页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81274180)

摘　　要：研究经典古方开心散类方定志小丸主要化学成分在抑郁模型大鼠体内的代谢产物,并归纳总结其代谢途径。通过慢性不可预知温和刺激(CUMS)建立抑郁大鼠模型,灌胃给予大鼠定志小丸提取液后,收集血液、胆汁、尿液、粪便并进行预处理,采用UPLC-Q-TOF-MSE技术进行检测,利用UPLC C18色谱柱,以乙腈-0.1%甲酸水溶液为流动相进行梯度洗脱,在负离子模式下获得MS/MSE质谱信息,通过对比空白与含药样品的液质数据,利用Metabolynx代谢产物分析软件处理,最终对定志小丸中9个活性化合物在血浆、胆汁、尿液、粪便中的33个代谢产物进行推测,并总结了其体内代谢途径。其中从大鼠血浆中鉴定了代谢产物3个,胆汁中鉴定3个,尿液和粪便中鉴定代谢产物共27个。为阐明定志小丸在体内发挥疗效的药效物质基础和作用机制提供依据。Dingzhi Xiaowan is a widely used traditional Chinese medicine in treating depression, which is a similar formula of Kaixinsan. In this research, a rapid ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF/MSE） method was established to analyze the metabolites of Dingzhi Xiaowan in depressive model rat plasma, bile, urine and feces. After we established Chronic unpredictable mild stress （CUMS） model rats and orally administrated Dingzhi Xiaowan, rat plasma, bile, urine and feces samples were collected and prepared. Using Waters Cortects UPLC C18 column（2.1 mm×50 mm, 1.6 μm）, acetonitrile-0.1% formic acid mobile phase gradient, these samples were analyzed and 33 metabolites of nine bioactive compounds were detected and tentatively identified by Metabolynx. Among the 33 metabolites, three metabolites were identified from plasma sample, three came from bile sample, and 27 metabolites were identified from urine and feces samples. This approach provided a rapid method for characterizing the metabolites of Dingzhi Xiaowan and gave the truly active structures and the action mechanism of their antidepressant effects.

关 键 词：定志小丸 抑郁模型 UPLC-Q-TOF-MSE 代谢产物 

分 类 号：R285.5[医药卫生—中药学]