苍附导痰汤治疗多囊卵巢综合征大鼠的血清代谢组学和网络药理学研究  

Study on serum metabolomics and network pharmacology of Cangfu Daotan decoction treating polycystic ovary syndrome in rats

作　　者：谢军[1] 解达帅 杨伟[2] 马乐[2] 姚宏军[1] 石萍 XIE Jun;XIE Dashuai;YANG Wei;MA Le;YAO Hongjun;SHI Ping(Department of Traditional Chinese Medicine,Yuncheng Central Hospital Affiliated to Shanxi Medical University,Yuncheng 044000,China;Department of Pharmacy,Yuncheng Central Hospital Affiliated to Shanxi Medical University)

机构地区：[1]山西医科大学附属运城市中心医院中医科,运城044000 [2]山西医科大学附属运城市中心医院药学部

出　　处：《山西医科大学学报》2024年第7期895-907,共13页Journal of Shanxi Medical University

基　　金：山西省教育厅高校科技创新计划项目(2020L0227)。

摘　　要：目的基于超高效液相色谱-四极杆-静电场轨道阱串联质谱(UHPLC-QE-MS)分析苍附导痰汤对多囊卵巢综合征大鼠血清中内源性标志物的影响,并结合网络药理学研究其发挥药效的作用通路。方法将40只大鼠随机分为正常组、模型组、达英-35组和苍附导痰组,每组10只。采用来曲唑法诱导多囊卵巢综合征(PCOS)大鼠模型,造模成功后,达英-35组给予达英-35灌胃,苍附导痰组给予苍附导痰汤灌胃,每天1次,连续28 d。ELISA法检测大鼠血清促卵泡生长激素(FSH)、促黄体生成素(LH)、睾酮(T)、雌二醇(E2)含量差异水平;苏木精-伊红(HE)染色法观察大鼠卵巢组织病理形态学变化;采用UHPLC-QE-MS分析各组大鼠血清样品,基于主成分分析法(PCA)及正交偏最小二乘判别分析法(OPLS-DA)筛选出相关差异代谢物,并依据MetaboAnalyst数据库查询相关代谢通路。采用网络药理学探究苍附导痰汤治疗多囊卵巢综合征的关键靶点,使用KEGG数据库富集分析作用通路,并借助MetScape插件构建“代谢物-反应-酶-基因”网络。结果与正常组相比,模型组大鼠血清中FSH含量明显上升(P<0.05),LH、T、E2含量显著上升(P<0.01);与模型组相比,达英-35组大鼠血清中LH、T、E2含量显著降低(P<0.01),苍附导痰组大鼠血清中T明显降低(P<0.05),LH、E2含量显著降低(P<0.01)。与模型组比较,达英-35组和苍附导痰组大鼠卵巢组织形态明显改善;代谢组学筛选15个苍附导痰汤治疗多囊卵巢综合征的差异代谢物,涉及类固醇激素生物合成、甘油磷脂代谢、精氨酸和脯氨酸代谢等途径。网络药理学分析显示苍附导痰汤治疗多囊卵巢综合征的核心靶点为AKT1、ESR1、EGFR等,KEGG富集显示涉及内分泌抵抗、类固醇合成、雌激素信号通路等;采用MetScape插件构建“代谢物-反应-酶-基因”网络,发现6个关键靶点CYP1B1、CYP19A1、AKR1C1、AKR1C3、HSD17B1、HSD17B2,以及涉及类固醇激�Objective To investigate the effects of Cangfu Daotan decoction on serum endogenous markers in rats with polycystic ovary syndrome(PCOS)by ultra-performance liquid chromatography-tandem Q exactive quadrupole-electrostatic field orbitrap mass spectro-metry(UHPLC-QE-MS),and explore its role pathway based on the network pharmacology.Methods Forty rats were randomly divided into four groups:normal group,model group,Daying-35 group,and Cangfu Daotan group,with 10 rats in each group.The PCOS models were induced by letrozole.After successful induction,the rats in Daying-35 group received Daying-35 by gavage once a day for 28 d,while the rats in Cangfu Daotan group were administered Cangfu Daotan decoction by gavage once a day for 28 d.ELISA was used to measure the serum levels of follicle-stimulating growth hormone(FSH),luteinizing hormone(LH),testosterone(T),and estradiol(E2)in rats.Hematoxylin-eosin(HE)staining was used to observe the pathomorphological changes of ovary in rats.UHPLC-QE-MS was used to analyze the serum samples of rats in each group.The relevant differential metabolites were screened based on principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA).The related metabolic pathways were searched according to the MetaboAnalyst database.Network pharmacology was used to explore the key targets of Cangfu Daotan decoction treating PCOS.KEGG database was utilized for pathway enrichment and analysis,and the"metabolite-reaction-enzyme-gene"network was constructed with the assistance of the MetScape.Results Compared with normal group,the serum FSH content was significantly increased in model group(P<0.05),and the contents of LH,T,and E2 were also significantly increased(P<0.01).Compared with model group,the serum contents of LH,T,and E2 were significantly reduced in Daying-35 group(P<0.01),and the serum T level was significantly reduced(P<0.05),and the contents of LH and E2 were also decreased in Cangfu Daotan group(P<0.01).Compared with model group,the morphology of ova

关 键 词：苍附导痰汤 多囊卵巢综合征 代谢组学 网络药理学 类固醇激素 生物合成 

分 类 号：R711[医药卫生—妇产科学]