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基于UPLC-MS/MS联用微透析技术的三七总皂苷在帕金森病小鼠模型中的药动学和药效学研究
引用本文:李新悦,吴玉梅,任静,马丽,刘静静,张兵,郭盼,刘志东. 基于UPLC-MS/MS联用微透析技术的三七总皂苷在帕金森病小鼠模型中的药动学和药效学研究[J]. 中草药, 2019, 50(13): 3119-3126
作者姓名:李新悦  吴玉梅  任静  马丽  刘静静  张兵  郭盼  刘志东
作者单位:天津中医药大学, 现代中药发现与制剂技术教育部工程中心, 天津 301617;天津中医药大学, 天津市现代重点实验室-省部共建国家重点实验室培育基地, 天津 301617,天津中医药大学, 现代中药发现与制剂技术教育部工程中心, 天津 301617;天津中医药大学, 天津市现代重点实验室-省部共建国家重点实验室培育基地, 天津 301617,天津中医药大学, 现代中药发现与制剂技术教育部工程中心, 天津 301617;天津中医药大学, 天津市现代重点实验室-省部共建国家重点实验室培育基地, 天津 301617,天津中医药大学, 现代中药发现与制剂技术教育部工程中心, 天津 301617;天津中医药大学, 天津市现代重点实验室-省部共建国家重点实验室培育基地, 天津 301617,天津中医药大学, 现代中药发现与制剂技术教育部工程中心, 天津 301617;天津中医药大学, 天津市现代重点实验室-省部共建国家重点实验室培育基地, 天津 301617,天津中医药大学, 现代中药发现与制剂技术教育部工程中心, 天津 301617;天津中医药大学, 天津市现代重点实验室-省部共建国家重点实验室培育基地, 天津 301617,天津中医药大学, 现代中药发现与制剂技术教育部工程中心, 天津 301617;天津中医药大学, 天津市现代重点实验室-省部共建国家重点实验室培育基地, 天津 301617,天津中医药大学, 现代中药发现与制剂技术教育部工程中心, 天津 301617;天津中医药大学, 天津市现代重点实验室-省部共建国家重点实验室培育基地, 天津 301617
基金项目:天津市自然科学基金项目(16ZXHLGX00170)
摘    要:目的探究1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病(PD)模型小鼠以三七总皂苷干预后,脑微透析液中三七皂苷R1(R1)、人参皂苷Rg1(Rg1)和氨基酸神经递质的含量变化。方法给小鼠ip MPTP造成PD小鼠模型,经iv三七总皂苷(PNS)溶液后,采用微透析技术采集脑微透析液。将样品分为2部分,一部分采用UPLC-MS/MS对R1和Rg1进行药动学研究,另一部分采用氨基酸柱前衍生化和HPLC-FLD进行药效学研究。结果小鼠iv PNS后,脑微透析液中R1的峰浓度(Cmax)为(35.48±24.4)ng/mL,Rg1的Cmax为(75.61±41.35)ng/m L。R1和Rg1的达峰时间(tmax)均为1.75 h。R1和Rg1的药时曲线下面积(AUC)分别为(100.12±84.29)ng·h/m L和(218.84±144.73)ng·h/m L。且给予PNS后的PD模型小鼠体内天冬氨酸和谷氨酸浓度降低,甘氨酸、牛磺酸和γ-氨基丁酸浓度增加。结论 PNS能一定程度透过血脑屏障(BBB)进入脑内,调节PD模型小鼠体内氨基酸水平的失衡,进而发挥神经保护作用。

关 键 词:三七总皂苷  药动学  药效学  帕金森病  微透析技术  氨基酸
收稿时间:2018-12-28

Pharmacokinetics and pharmacodynamics study of Panax notoginseng saponins in mice with Parkinson's disease by using UPLC-MS/MS combined with microdialysis
LI Xin-yue,WU Yu-mei,REN Jing,MA Li,LIU Jing-jing,ZHANG Bing,GUO Pan and LIU Zhi-dong. Pharmacokinetics and pharmacodynamics study of Panax notoginseng saponins in mice with Parkinson's disease by using UPLC-MS/MS combined with microdialysis[J]. Chinese Traditional and Herbal Drugs, 2019, 50(13): 3119-3126
Authors:LI Xin-yue  WU Yu-mei  REN Jing  MA Li  LIU Jing-jing  ZHANG Bing  GUO Pan  LIU Zhi-dong
Affiliation:Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China;Tianjin State Key Laboratory of Modern Chinese Medicine Province and Ministry Co-Established State Key Laboratory Cultivation Base, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China,Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China;Tianjin State Key Laboratory of Modern Chinese Medicine Province and Ministry Co-Established State Key Laboratory Cultivation Base, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China,Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China;Tianjin State Key Laboratory of Modern Chinese Medicine Province and Ministry Co-Established State Key Laboratory Cultivation Base, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China,Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China;Tianjin State Key Laboratory of Modern Chinese Medicine Province and Ministry Co-Established State Key Laboratory Cultivation Base, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China,Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China;Tianjin State Key Laboratory of Modern Chinese Medicine Province and Ministry Co-Established State Key Laboratory Cultivation Base, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China,Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China;Tianjin State Key Laboratory of Modern Chinese Medicine Province and Ministry Co-Established State Key Laboratory Cultivation Base, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China,Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China;Tianjin State Key Laboratory of Modern Chinese Medicine Province and Ministry Co-Established State Key Laboratory Cultivation Base, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China and Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China;Tianjin State Key Laboratory of Modern Chinese Medicine Province and Ministry Co-Established State Key Laboratory Cultivation Base, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
Abstract:
Keywords:Panax notoginseng saponins  pharmacokinetics  pharmacodynamics  Parkinson''s disease  microdialysis  amino acids
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