补阳还五汤抗脑缺血损伤药效物质基础的血清药物化学研究  

A Serum Pharmacochemical Study on the Pharmacodynamic Substances Basis of the Anti-Ischemic Injury of Buyang Huanwu Decoction

作　　者：曾珂琪 周欣 聂聪 张英丰[1] ZENG Keqi;ZHOU Xin;NIE Cong;ZHANG Yingfeng(School of Chinese Materia Medica,Guangzhou University of Chinese Medicine,Guangzhou 510006 Guangdong,China)

机构地区：[1]广州中医药大学中药学院,广东广州510006

出　　处：《中药新药与临床药理》2023年第9期1227-1235,共9页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金项目(81873227)。

摘　　要：目的基于血清药物化学方法探讨补阳还五汤抗脑缺血损伤的药效物质基础。方法采用真空冷冻干燥法制备补阳还五汤水煎液冻干粉。采用线栓法复制大脑中动脉阻塞(MCAO)大鼠模型,按照生药5.4 g·kg^(-1)剂量灌胃补阳还五汤冻干粉药液,每日1次,连续给药7 d。末次给药后分离模型组及给药组大鼠的血清和脑组织,经前处理后采用超高效液相色谱四级杆飞行时间质谱联用(UPLC-Q-TOF-MS)方法,以0.1%甲酸水溶液-乙腈梯度洗脱后,在正、负离子模式下检测。通过补阳还五汤冻干粉及血清、脑组织样品分析所得一、二级质谱数据,结合Chemicalbook和PubChem数据库及相关文献信息,对入血、入脑成分进行综合指认;通过CFM-ID 4.0软件对成分结构断裂方式进行预测;通过TCMSP数据库对指认所得入血、入脑成分来源药材进行归属。结果共指认出芒柄花素、毛蕊异黄酮、黄芪甲苷、芍药新苷等89个化学成分,其中包括黄芪甲苷、毛蕊异黄酮苷等44个入血成分,毛蕊异黄酮、洋川芎内酯A等24个入脑成分,以及黄芪甲苷、藁本内酯、毛蕊异黄酮、芍药新苷、二氢猕猴桃内酯、洋川芎内酯I等16种同时入血入脑成分。结论入血、入脑活性成分可能是补阳还五汤抗脑缺血损伤,发挥神经保护效应的潜在药效物质基础。ObjectiveTo investigate the pharmacodynamic substances basis of the anti-ischemic injury effect of Buyang Huanwu Decoction based on serum pharmacochemical study.MethodsThe freeze-dried powder of Buyang Huanwu Decoction was prepared by vacuum freeze-drying method.A rat model of middle cerebral artery occlusion(MCAO)was replicated using the suture-occluded method,and the freeze-dried powder of Buyang Huanwu Decoction was administered by gavage at a dose of 5.4 g·kg-1of the raw drug once a day for 7 consecutive days.The serum and brain tissues of rats in the model group and the administration group were separated after the last administration and detected by using the UPLC-Q-TOF-MS method after pre-treatment and elution by the gradient of 0.1%aqueous formic acid-acetonitrile.The serum and brain tissues of rats detected in positive and negative ion modes.The primary and secondary mass spectrometry data obtained from the analysis of the freeze-dried powder of Buyang Huanwu Decoction,serum and brain tissue samples were combined with the Chemicalbook and PubChem databases and relevant literature information to comprehensively identify the components of blood and brain.The structural fracture modes of the components were predicted by using the software of CFM-ID 4.0.The source of the identified blood and brain absorption components was attributed to the herbs through the TCMSP database.ResultsA total of 89 constituents were identified,including formononetin,calycosin,astragaloside and lactiflorin,including 44 blood-entering constituents such as astragaloside and calycosin,24 brain absorption components such as calycosin and senkyunolide A,and 16 simultaneous blood-entering and brain absorption components such as astragaloside,ligustilide,calycosin,lactiflorin,dihydroactinidiolide,senkyunolide I.ConclusionThe blood-and brain-entering active components may be the potential pharmacological substances basis for the anti-ischemic injury and neuroprotective effect of Buyang Huanwu Decoction.

关 键 词：补阳还五汤 血清药物化学 缺血性脑卒中 超高效液相色谱四级杆飞行时间质谱联用 入血成分 入脑成分 大鼠 

分 类 号：R285.5[医药卫生—中药学] R284.1[医药卫生—中医学]