中风停颗粒对急性脑缺血模型大鼠代谢组学的影响  

Effect of Zhongfengting Granule on Metabolomics of Acute Cerebral Ischemia Model Rats

作　　者：董珍宇[1] 朱文浩[2] 孙新月 英振昊[3] 蒲馨颖 郭大千 门伟业 DONG Zhenyu;ZHU Wenhao;SUN Xinyue;YING Zhenhao;PU Xingying;GUO Daqian;MEN Weiye(Beijing Chao-yang Hospital,Capital Medical University,Beijing 100020,China;Zibo Hospital of Traditional Chinese Medicine,Zibo 255399,China;Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Binzhou Hospital of Traditional Chinese Medicine,Binzhou 256601,China;Linyi Hospital of Traditional Chinese Medicine,Linyi 276037,China)

机构地区：[1]首都医科大学附属北京朝阳医院,北京100020 [2]淄博市中医医院,淄博255399 [3]山东中医药大学,济南250355 [4]山东省滨州市中医医院,滨州256601 [5]临沂市中医医院,临沂276037

出　　处：《世界科学技术-中医药现代化》2025年第2期564-572,共9页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家中医药管理局第五批全国中医临床优秀人才研修项目(国中医药人教函[2022]1号),负责人:朱文浩;国家中医药管理局科技司共建科技项目(GZY-KJS-SD-2023-008):基于证候要素辨证探讨中风停颗粒通过PI3K/Akt/m TOR通路抑制脑梗死后炎症损伤的机制研究,负责人:朱文浩;山东省中医药科技面上项目(M-2023066):基于代谢组学和蛋白组学的熄风清火活血化痰汤治疗急性缺血性中风有效成分和机制研究,负责人:朱文浩。

摘　　要：目的应用非靶向代谢组学技术探究中风停颗粒对急性脑缺血MCAO模型大鼠血浆代谢产物的影响,以阐明中风停颗粒神经保护作用机制。方法将24只雄性SD大鼠随机分为空白组、模型组和中药组,每组8只。模型组、中药组采用大脑中动脉线栓法建立MCAO大鼠模型,造模成功后当天给药,中药组给予(22.68 g·kg^(-1))中风停颗粒药液进行灌胃,空白组、模型组给予等体积生理盐水,干预7 d。给药结束后静脉取血,采用超高效液相色谱-四级杆串联飞行时间质谱仪分析空白组、模型组、中药组大鼠血浆样品,并采用多元统计分析筛选差异代谢产物;基于京都基因与基因组百科全书(KEGG)数据库对筛选出的差异代谢物进行代谢通路分析。结果多元统计分析结果显示,急性脑缺血大鼠模型体内的22个潜在生物标志物含量发生了显著变化,中风停颗粒对上述22个潜在生物标志物进行了显著回调(P<0.05)。代谢通路富集结果显示,中风停颗粒主要影响了苯丙氨酸代谢、酪氨酸代谢、抗坏血酸代谢、花生四烯酸代谢。结论急性脑缺血MCAO模型大鼠体内代谢物及代谢通路发生改变,中风停颗粒可回调差异代谢物及代谢通路,主要涉及苯丙氨酸代谢等,还参与调节能量代谢。Objective To investigate the effects of Zhongfengting granule on plasma metabolites in acute cerebral ischemia MCAO model rats by non-targeted metabolomics techniques,and to elucidate the neuroprotective mechanism of Zhongfengting granule.Methods 24 male SD rats were randomly divided into blank group,model group and Chinese medicine group,with 8 rats in each group.Model group and Chinese medicine group were treated with middle cerebral artery thrombus method to establish the MCAO rat model,and the medicine was administered on the same day after the successful modeling.The Chinese medicine group was given(22.68 g·kg^(-1))Zhongfengting granule solution by gavage,and the blank group and model group were given equal volume normal saline for 7 days.After administration,blood was collected intravenously.Plasma samples from blank group,model group and Chinese medicine group were analyzed by ultra-high performance liquid chromatogre-quadrupole tandem time-of-flight mass spectrometer,and differential metabolites were screened by multivariate statistical analysis.The metabolic pathways of the differentiated metabolites were analyzed based on KEGG database.Results Multivariate statistical analysis showed that the content of 22 potential biomarkers in the rat model of acute cerebral ischemia had significant changes,and the above-mentioned 22 potential biomarkers were significantly reversed by Zhongfengting granule(P<0.05).The enrichment results of metabolic pathways showed that Zhongfengting granule mainly affected phenylalanine metabolism,tyrosine metabolism,ascorbic acid metabolism and arachidonic acid metabolism.Conclusion Metabolites and metabolic pathways in MCAO model rats with acute cerebral ischemia are changed,and the different metabolites and metabolic pathways can be reversed by Zhongfengting granule,which mainly involve phenylalanine metabolism and regulate energy metabolism.

关 键 词：中风停颗粒 代谢组学 急性脑缺血 MCAO大鼠 氨基酸代谢 

分 类 号：R285.5[医药卫生—中药学]