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中国医药导刊 ›› 2025, Vol. 27 ›› Issue (5): 497-506.

• 基础研究 • 上一篇    下一篇

LC-MS法比较益心饮有效成分在正常与房颤大鼠心/血中的药时曲线特征

李娟12a, 赵青3, 梁静蕾4, 唐婷婷2a, 栏目名称:杨丽媛4, 庞涛2a, 李峻2b, 陈卫东1*, 张凤2a*   

  1. 1.安徽中医药大学,安徽 合肥 230012;
    2.海军军医大学第二附属医院 药剂科a,康复医学科b,上海 200003;
    3.上海静安区闸北中心医院药剂科,上海 200070;
    4.上海中医药大学,上海 201203
  • 收稿日期:2025-02-14 修回日期:2025-04-28 接受日期:2025-06-09 出版日期:2025-05-28 发布日期:2025-07-23
  • 基金资助:
    国家科技部重点研发计划(2022YFC3501700);上海市科学技术委员会(22S21901900);上海中医药大学有组织科研重点专项(2023YZZ02);海军军医大学“深蓝”工程远航人才计划(SL-33)

Comparison of Time-Concentration Characteristics of Active Ingredients from Yixinyin in Plasma and Heart Samples of Normal and Atrial Fibrillation Rats by LC-MS

LI Juan1,2a, ZHAO Qing3, LIANG Jinglei4, TANG Tingting2a, YANG Liyuan4, PANG Tao2a, LI Jun2b#br# #br#   

  1. 1.Anhui University of Chinese MedicineAnhui Hefei 230012, China
    2.Department of Pharmacya Department of Rehabilitation Medicineb Changzheng Hospital
    Naval Medical University Shanghai 200003, China
    3.Department of Pharmacy Zhabei Center Hospital Jing'an District Shanghai 200070, China
    4 Shanghai University of Traditional Chinese Medicine Shanghai 201203, China
  • Received:2025-02-14 Revised:2025-04-28 Accepted:2025-06-09 Online:2025-05-28 Published:2025-07-23

摘要:

目的:基于液质联用技术探讨益心饮在正常和房颤大鼠血浆及心脏移行成分的时量特征。方法:连续30 d用酒精液体饲料饲喂大鼠,检测心超确定左心房扩张后,采用连续7 d尾静脉注射药物乙酰胆碱-氯化钙促使大鼠心房电活动紊乱,造成房颤模型。大鼠随机分为正常组、模型组、正常+益心饮组、模型+益心饮组。益心饮给药剂量为31 g·kg-1·d-1,不给药组给予同体积0.9% NaCl溶液。连续灌胃14 d后采集多个时间点的全血,以及终点的心脏组织,采用超高效液相色谱-四极杆-飞行时间质谱(UHPLC-Q-TOF/MS)技术检测各组大鼠血浆、心脏组织的移行成分。结果:与正常组比较,模型组房颤诱发率、房颤易感性、房颤持续时间显著升高(P<0.05),提示造模成功。益心饮体外鉴定得111种化学成分,正常及房颤大鼠血浆、心脏分别均可检测到27种、8种化学成分。时量特征结果表明4-羟基肉桂酸、香兰素、丹酚酸B、芒柄花苷、大豆黄素、毛蕊异黄酮、异甘草素、肉豆蔻醚、洋川芎内酯A、甘草次酸在房颤大鼠血浆中含量较高;甘草苷、毛蕊异黄酮苷、姜辣素等8种成分还可在心脏组织中被检测到。结论:靶向入心成分甘草苷、毛蕊异黄酮苷、姜辣素可能是益心饮治疗房颤的关键药效成分。

 

关键词: 益心饮, 房颤, 超高效液相色谱-四极杆-飞行时间质谱, 甘草苷, 毛蕊异黄酮苷, 姜辣素

Abstract:

Objective: To investigate the time-concentration characteristics of the plasma and cardiac migratory components of Yixinyin in normal and atrial fibrillation rats based on liquid chromatography-mass spectrometry technology.Methods: Rats were fed with an alcohol-liquid diet for 30 consecutive days and left atrial dilation was confirmed by echocardiography. Subsequently atrial fibrillation AF model was induced by continuous 7-day tail vein injection of acetylcholine-calcium chloride. Rats were randomly divided into four groups normal group model group normal+ Yixinyin group and model+Yixinyin group. Yixinyin was administered at a dose of 31 g·kg-1·d-1 while non-treated two groups received an equivalent volume of saline. After 14 consecutive days of intragastric administration whole blood samples were collected at multiple time points and cardiac tissues were harvested at the endpoint. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was employed to detect the migrating components in the tested samples.Results: Compared with the normal group the rate of atrial fibrillation induction susceptibility to atrial fibrillation and duration of atrial fibrillation were significantly higher in the model group P < 0.05), suggesting successful modeling. In vitro 111 chemical components were identified in Yixinyin and 27 and 8 chemical components were detected in plasma and heart of normal and atrial fibrillation rats respectively. The time-concentration profile results indicated that 4-hydroxycinnamic acidvanillinsalicylic acid B ononin daidzein calycosin isoliquiritigenin myristicin senkyunolide A and glycyrrhetinic acid were present at higher levels in the plasma of AF rats. Additionally eight components including liquiritin calycosin 7-glucoside and gingerol were also detected in heart tissue species.Conclusion: The targeted cardiac components namely liquiritin calycosin-7-glucoside and gingerol may serve as the key pharmacologically active constituents of Yixinyin in the treatment of AF.


Key words: Yixinyin , Atrial fibrillation , UHPLC-Q-TOF/MS , Liquiritin , Calycosin 7-glucoside , Gingerol