基于转录组学联合代谢组学探究鸡骨草防治肝纤维化的分子机制  

Exploring the molecular mechanism of Arbus Herb against liver fibrosis based on transcriptomics combined with metabolomics

作　　者：郑洋 王佳慧 张鸿霖 赵铁建 钟卓妍 黄娜[1] 梁天坚[1] 罗伟生[3] 汪磊[1,3] ZHENG Yang;WANG Jia-hui;ZHANG Hong-lin;ZHAO Tie-jian;ZHONG Zhuo-yan;HUANG Na;LIANG Tian-jian;LUO Wei-sheng;WANG Lei(Department of Medicine,Faculty of Chinese Medicine Science of Guangxi University of Chinese Medicine,Nanning 530222,China;School of Basic Medicine,Guanxi University of Chinese Medicine,Nanning 530222,China;School of Graduate Studies,Guangxi University of Chinese Medicine,Nanning,530222,China)

机构地区：[1]广西中医药大学赛恩斯新医药学院,广西南宁530222 [2]广西中医药大学基础医学院,广西南宁530222 [3]广西中医药大学研究生学院,广西南宁530222

出　　处：《时珍国医国药》2025年第1期193-200,共8页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金(81960751,82204755);广西自然科学基金青年基金项目(2023GXNSFBA026274,2024GXNSFAA01023);广西研究生教育创新计划基金资助项目(YCBZ2024150);广西壮瑶药重点实验室基金资助项目(GXZYYKF2023-05);广西中医药大学赛恩斯新医药学院科研项目(2022CX004,2023MS008,2024ZZA003,2024ZZB007);广西中医药大学自治区级大学生创新创业训练项目(S202410600145);广西中医药大学赛恩斯新医药学院国家级大学生创新创业训练项目(202413643009)。

摘　　要：目的借助转录组学联合代谢组学揭示鸡骨草防治肝纤维化的潜在机制。方法借助四氯化碳构建肝纤维化模型,将小鼠分为三组即空白组、模型组和鸡骨草组;HE和Masson染色以及肝功能检测肝组织病理改变;转录组学检测差异基因表达情况;代谢组学检测差异代谢物表达情况;转录组学与代谢组学联合分析;分子生物学检测差异基因。结果HE和Masson染色以及肝功能检测发现鸡骨草显著改善肝脏病理改变;转录组学发现鸡骨草组与模型组差异基因1471个,差异基因富集分析发现其主要位于细胞周期、亚油酸、花生四烯酸、PI3K/AKT等信号通路上;代谢组学发现鸡骨草组与模型组差异鸡骨草组与模型组差异代谢物177个,差异代谢物富集分析发现其主要位于花生四烯酸、亚油酸、丙酮酸代谢、色氨酸代谢等通路上;鸡骨草组与模型组差异基因与差异代谢组关联分析发现模型关联度较好,且主要位于花生四烯酸和亚油酸等通路上;分子生物学检测发现鸡骨草显著抑制ALOX15和PTGDS分子表达。结论鸡骨草抑制ALOX15和PTGDS分子表达,调控花生四烯酸代谢,可能是其抗肝纤维化的重要分子机制。Objective To reveal the potential mechanism of Arbus Herb against hepatic fibrosis with transcriptomics and metabolomics.Methods The liver fibrosis model was constructed with carbon tetrachloride,and mice were divided into three groups,i.e.,the blank group,the model group and the Arbus Herb group;HE and Masson stainings as well as liver function were used to detect liver histopathological alterations;transcriptomics was used to detect differential gene expression;metabolomics was used to detect differential metabolite expression;transcriptomics and metabolomics were used to conduct joint analysis;and molecular biology was used to detect differential genes.Results HE and Masson stainings as well as liver function tests found that Arbus Herb significantly improved the liver pathological conditions;transcriptomics found that 1471 genes differed between the Arbus Herb group and the model group,and the enrichment analysis of differential genes found that they were mainly located in the cell cycle,linoleic acid,arachidonic acid,PI3K/AKT and other signalling pathways;Metabolomics revealed 177 different metabolites between the Abrus Herb group and the model group.Differential metabolite enrichment analysis revealed that they were mainly located in the pathways of arachidonic acid,linoleic acid,pyruvic acid metabolism,and tryptophan metabolism;differential gene and differential metabolome association analysis between the Arbus Herb group and the model group found that the model association was better and mainly located in pathways such as arachidonic acid and linoleic acid;molecular biology testing found that Arbus Herb significantly inhibited the expression of molecules of ALOX15 and PTGDS.Conclusion Inhibition of ALOX15 and PTGDS molecular expression and regulation of arachidonic acid metabolism by Arbus Herb may be a significant molecular mechanism for its anti-hepatic fibrosis.

关 键 词：鸡骨草 转录组学 代谢组学 肝纤维化 花生四烯酸 

分 类 号：R285.5[医药卫生—中药学]