基于GC-MS的血清代谢组学探究夏枯草茎叶酚酸抗慢性盆腔炎的作用机制  

Mechanism of action of phenolic acids in the stems and leaves of Prunella vulgaris L.against chronic pelvic inflammatory disease based on serum metabolomics using GC-MS

作　　者：李珊 谭知浩 肖志葵 熊苏慧 罗弘杉 谢菁琛[1,2] 林丽美 LI Shan;TAN Zhihao;XIAO Zhikui;XIONG Suhui;LUO Hongshan;XIE Jingchen;LIN Limei(School of Pharmacy,Hunan University of Chinese Medicine,Changsha,Hunan 410208,China;Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province,Changsha,Hunan 410208,China)

机构地区：[1]湖南中医药大学药学院,湖南长沙410208 [2]湘产大宗药材品质评价湖南省重点实验室,湖南长沙410208

出　　处：《湖南中医药大学学报》2024年第2期235-244,共10页Journal of Hunan University of Chinese Medicine

基　　金：湖南省教育厅重点项目(20A380);湖南省自然科学基金项目(2022JJ80085,2022JJ80020);湖南省卫生健康委员会科研计划课题项目(202113051481)。

摘　　要：目的基于GC-MS的血清代谢组学探究夏枯草茎叶酚酸抗慢性盆腔炎的有效成分及其作用机制。方法本实验采用60只雌性大鼠,采用混合菌液加机械损伤对40只大鼠进行慢性盆腔炎造模处理,正常组10只大鼠不做处理,假手术组10只大鼠只做机械损伤。造模成功后,将模型大鼠分为模型组、康妇炎胶囊组、头孢克洛分散片组和夏枯草茎叶酚酸组,每组10只,连续给药21 d;取正常组、假手术组、模型组和夏枯草茎叶酚酸组、康妇炎胶囊组、头孢克洛分散片组大鼠血清进行代谢组学分析,并对筛选后的差异表达基因进行GO功能分析和KEGG通路富集分析。结果夏枯草茎叶酚酸能修复慢性盆腔炎组织病理损伤;代谢组学鉴定出47种代谢物,主要以糖类、氨基酸、有机酸、脂肪酸、多元醇等多种内源性物质为主;多因素分析表明,夏枯草可改善炎症大鼠血清代谢产物异常。主要差异代谢通路为氨基酸代谢、抗坏血酸和醛糖二酸代谢途径,主要差异代谢物为尿素、葡萄糖酸、D-葡萄糖醛酸、L-赖氨酸、甘氨酸、L-丝氨酸、L-苏氨酸、L-脯氨酸、L-苯丙氨酸等,还影响机体苯丙氨酸、酪氨酸和色氨酸生物合成,抗坏血酸和醛糖二酸代谢,苯丙氨酸代谢,花生四烯酸代谢,甘氨酸、丝氨酸和苏氨酸代谢。GO功能分析表明,对激素的反应、细胞对氮化合物的反应和磷酸化的正向调节等是主要参与的生物过程。KEGG通路富集结果显示,PI3K-Akt信号通路、甲状腺激素信号通路和内分泌抵抗等为主要富集的通路。结论夏枯草茎叶酚酸对慢性盆腔炎大鼠具有明显的治疗作用,其机制可能与作用于COBT、ADH1C、MAOB等靶点,干预PI3K-Akt信号通路、甲状腺激素信号通路和内分泌抵抗等信号通路,引起差异代谢物变化有关。Objective To explore the active ingredients and mechanism of action of phenolic acids in the stems and leaves of Prunella vulgaris L.against chronic pelvic inflammatory disease based on serum metabolomics using GC-MS.Methods A total of 60 female rats were used in this experiment.Among them,40 rats were treated with mixed bacterial liquid and mechanical injury to establish chronic pelvic inflammatory disease model,ten rats in the normal group were not treated,and ten rats in the sham-operated group were only treated with mechanical injury.After successful modeling,the rat models were subdivided into model group,Kangfuyan Capsules group(KFY group),Cefaclor Dispersible Tablets group(CEC group),and group of phenolic acids from stems and leaves of Prunella vulgaris L.(XKC group).Each group was administered with the corresponding medication or distilled water continuously for 21 d.The rat serum from the normal,sham-operated,model,and XKC groups,KFY group,CEC group was analyzed using metabolomics,and the differentially expressed genes after screening were analyzed by GO function and KEGG pathway enrichment.Results The phenolic acids in the stems and leaves of Prunella vulgaris L.could repair the pathological damage of chronic pelvic inflammatory tissue.Metabolomics identified 47 metabolites,mainly including carbohydrates,amino acids,organic acids,fatty acids,polyols,and other endogenous substances,and multifactor analysis showed that Prunella vulgaris L.could reduce the abnormal serum metabolites in the inflammatory rats.The main differential metabolic pathways are amino acid metabolism,as well as ascorbic acid and aldaric acid metabolism.The main differential metabolites are urea,gluconic acid,D-glucuronic acid,L-lysine,glycine,L-serine,L-threonine,L-proline,L-phenylalanine,etc.The disease also affected the biosynthesis of phenylalanine,tyrosine,and tryptophan,ascorbic acid and aldaric acid metabolism,phenylalanine metabolism,arachidonic acid metabolism,as well as glycine,serine,and threonine metabolism.GO function ana

关 键 词：夏枯草茎叶 酚酸 慢性盆腔炎 血清代谢组学 气相色谱-质谱法 

分 类 号：R284.1[医药卫生—中药学]