基于血清代谢组学探究川芎-香附药对调控色氨酸通路治疗偏头痛的作用机制  

Serum Metabolomics Reveals the Mechanism of Chuanxiong Rhizoma-Cyperi Rhizoma in Regulating Tryptophan Metabolism Pathway in the Treatment of Migraine

作　　者：晋林立 张英砾 吴莎[1,2] JIN Linli;ZHANG Yingli;WU Sha(School of Traditional Chinese Medicine,Capital Medical University,Beijing 100069,China;Beijing Key Laboratory of Traditional Chinese Medicine Collateral Disease Theory Research,Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学中医药学院,北京100069 [2]首都医科大学中医络病研究北京市重点实验室,北京100069

出　　处：《中国现代中药》2025年第3期488-497,共10页Modern Chinese Medicine

基　　金：国家自然科学基金项目(82474380);北京市教育委员会科研计划项目(KM202210025020);北京市属高校教师队伍建设支持计划优秀青年人才项目(BPHR202203112)。

摘　　要：目的:基于血清代谢组学探究川芎-香附药对治疗偏头痛的作用机制。方法:雄性SD大鼠,皮下注射硝酸甘油制备急性偏头痛模型,随机分为对照组、模型组、阳性药组、川芎-香附组、川芎组、香附组。腹主动脉取血,分离血清和脑干,超高效液相色谱串联质谱法进行血清代谢组学分析,筛选差异代谢物和差异代谢通路。使用Metascape插件构建代谢物-反应-酶-基因网络,分析差异性代谢物和差异性代谢通路的靶基因。逆转录实时定量聚合酶链式反应(RT-qPCR)检测色氨酸羟化酶2(TPH2) mRNA表达,酶联免疫吸附测定法(ELISA)检测TPH2和5-羟色胺(5-HT)含量。结果:各组大鼠血清代谢轮廓存在明显差异,川芎-香附、川芎、香附治疗偏头痛的差异性代谢物分别有25、7、13个,川芎-香附抗偏头痛的差异性代谢通路是泛醌和其他萜醌类生物合成、生物素代谢、色氨酸代谢通路,川芎抗偏头痛的差异性代谢通路是生物素代谢通路,香附抗偏头痛的差异性代谢通路是色氨酸代谢通路。色氨酸代谢通路的关键靶基因是TPH2,其参与5-HT代谢。验证实验发现,模型组大鼠脑干中TPH2mRNA表达量降低、TPH2和5-HT-含量显著降低,川芎-香附组、香附组可显著升高TPH2 mRNA表达量、TPH2和5-HT含量,川芎组升高TPH2 mRNA表达量、TPH2和5-HT含量但不显著。结论:川芎-香附药对通过调控色氨酸代谢及其下游靶基因TPH2的表达而促进5-HT的合成,实现治疗偏头痛的配伍增效作用。Objective:To explore the mechanism of the herb pair Chuanxiong Rhizoma-Cyperi Rhizoma in the treatment of migraine based on serum metabolomics.Methods:Male SD rats were randomized into control,model,positive drug,Chuanxiong Rhizoma-Cyperi Rhizoma,Chuanxiong Rhizoma,and Cyperi Rhizoma groups.The rats in other groups except the control group received subcutaneous injection with nitroglycerin for the modeling of acute migraine.Blood was collected from the abdominal aorta,and the serum was analyzed by metabolomics through ultra-performance liquid chromatography mass spectrometry,on the basis of which differential metabolites and metabolic pathways were screened.A compound-reaction-enzyme-gene network was constructed by the Metascape plugin for screening the targets of differential metabolites and metabolic pathways.Reverse transcription-polymerase chain reaction(RT-PCR)was employed to determine the mRNA level of tryptophan hydroxylase 2(TPH2).The levels of TPH2 and 5-hydroxytryptamine(5-HT)were measured by enzyme-linked immunosorbent assay(ELISA).Results:There were significant differences in the serum metabolic profiles among groups.A total of 25,7,and 13 differential metabolites were identified for Chuanxiong Rhizoma-Cyperi Rhizoma,Chuanxiong Rhizoma,and Cyperi Rhizoma,respectively,in treating migraine.Ubiquinone and other terpenoid-quinone biosynthesis,biotin metabolism,and tryptophan metabolism were identified as the key metabolic pathways for Chuanxiong Rhizoma-Cyperi Rhizoma in treating migraine.Biotin metabolism and tryptophan metabolism were identified as the key metabolic pathways for Chuanxiong Rhizoma and Cyperi Rhizoma,respectively,in treating migraine.TPH2 involved in 5-HT metabolism was the key target gene of the tryptophan metabolic pathway.Validation experiments showed that the mRNA level of TPH2 and the levels of TPH2 and 5-HT were significantly decreased in the brainstem tissue of migraine rats.Compared with the model group,Chuanxiong Rhizoma-Cyperi Rhizoma and Cyperi Rhizoma significantly up-regulat

关 键 词：川芎 香附 偏头痛 代谢组学 色氨酸 

分 类 号：R285[医药卫生—中药学]