去氢骆驼蓬碱体外抗细粒棘球蚴的非靶向代谢组学研究  

Non-targeted metabolomics research of harmine anti-Echinococcus granulosus in vitro

作　　者：徐勤伟 高惠静 卡地尔亚·库尔班[1] 马芹 滕亮 XU Qin-wei;GAO Hui-jing;KADIERYA Ku-er-ban;MA Qin;TENG Liang(College of Pharmacy,Xinjiang Medical University,Urumqi 83001l,Xinjiang Uygur Autonomous Region,China;State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia,Urumqi830054,XinjiangUygur Autonomous Region,China;Department of Pharmacy,The First Afiliated Hospital of Xinjiang Medical University,Urumqi 830054,Xinjiang Uygur Autonomous Region,China;Xinjiang Huashidan Pharmaceutical Co.,Ltd,Urumqi 83001l,Xinjiang Uygur Autonomous Region,China)

机构地区：[1]新疆医科大学药学院,新疆维吾尔自治区乌鲁木齐830011 [2]省部共建中亚高发病成因与防治国家重点实验室,新疆维吾尔自治区乌鲁木齐830054 [3]新疆医科大学第一附属医院药学部,新疆维吾尔自治区乌鲁木齐830054 [4]新疆华世丹药业股份有限公司,新疆维吾尔自治区乌鲁木齐830011

出　　处：《中国临床药理学杂志》2025年第3期361-365,共5页The Chinese Journal of Clinical Pharmacology

基　　金：省部共建中亚高发病成因与防治国家重点实验室开放课题基金资助项目(SKL-HIDCA-2022-BC3,SKL-HIDCA-2023-YX1);新疆维吾尔自治区重点研发基金资助项目(2022B03013-4);新疆维吾尔自治区自然科学基金资助项目(2023D01D16,2023D01A120);中华国际医学交流会基金会-中华医学会临床药学分会临床药学科研基金资助项目(Z-2021-46-2101-2023);兵团科技攻关计划基金资助项目(2023AB009-04)。

摘　　要：目的基于非靶向代谢组学研究去氢骆驼蓬碱(HM)抑制细粒棘球蚴的作用机制。方法将无菌培养的细粒棘球蚴分为空白组(KB组,常规培养)、溶剂组(DMSO组,DMSO 2μL)及给药组(HM组,20 mmoL·L^(-1)HM溶液2μL),干预48 h后伊红染色观察其存活率,扫描电镜观察其超微结构变化。同时,基于超高效液相色谱-质谱联用(UPLC-MS/MS)技术对各组细粒棘球蚴进行非靶向代谢组学分析,筛选差异代谢物,探究HM对细粒棘球蚴代谢谱的影响。结果伊红染色及扫描电镜结果显示,HM在体外对细粒棘球蚴具有明显的抑制作用。代谢组学结果显示,HM组与KB组共有15种具有显著差异的代谢物(均P<0.05)。将差异代谢物经京都基因与基因组百科全书(KEGG)富集后,结果显示HM主要影响细粒棘球蚴的氨基酸代谢、脂肪酸代谢及核苷酸代谢等代谢通路。结论HM对细粒棘球蚴具有显著的抑制作用,其机制可能与调节氨基酸代谢、脂肪酸代谢和核苷酸代谢等途径相关,可以为后续抗囊型包虫病药物靶点的开发提供新思路。Objective To investigate the mechanism of action of harmine(HM)in anti-Echinococcus granulosus(E.g)based on non-targeted metabolomics.Methods The aseptically cultured fine-grained E.g was divided into blank group(KB group,conventional culture),solvent group(DMSO group,DMSO 2μL)and administration group(HM group,20 mmoL·L^(-1)HM solution 2μL).Survival rate was observed by eosin staining after 48 h of intervention and the ultrastructural changes were observed by scanning electron microscopy,respectively.Meanwhile,non-targeted metabolomics analysis was performed based on ultra performance liquid chromatography-mass spectrometry(UPLC-MS/MS)technology on each group of E.g to screen the differential metabolites and explore the effect of harmine on the metabolic profile of E.g.Results Eosin staining and scanning electron microscopy results showed that harmine had a significant inhibitory effect on E.g in vitro.Metabolomics results showed that there were a total of 15 metabolites with significant differences between the harmine and blank groups(all P<0.05).Enrichment of the differential metabolites by Kyoto Encyclopedia of Genes and Genomes(KEGG)showed that harmine mainly affected the metabolic pathways of amino acid metabolism,fatty acid metabolism and nucleotide metabolism in E.g.Conclusion Harmine had a significant inhibitory effect on E.g,the mechanism of which may be related to the regulation of amino acid metabolism,fatty acid metabolism and nucleotide metabolism pathways,which can provide a new way of thinking for the development of the subsequent anti-cystic echinococlosis drug targets.

关 键 词：去氢骆驼蓬碱 非靶向代谢组学 细粒棘球蚴 氨基酸代谢 脂肪酸代谢 

分 类 号：R978.6[医药卫生—药品]