首页|代谢组学联合网络药理学分析香蜂草苷缓解非酒精性脂肪肝大鼠的作用机制

代谢组学联合网络药理学分析香蜂草苷缓解非酒精性脂肪肝大鼠的作用机制

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目的:利用非靶向代谢组学联合网络药理学研究香蜂草苷改善非酒精性脂肪性肝病(NAFLD)脂代谢的作用机制。方法:将大鼠随机分为正常组、模型组和香蜂草苷组。模型组与香蜂草苷组给予高脂饮食(HFD)8周诱导NAFLD动物模型。灌胃给药，连续8周。采用苏木精—伊红(HE)、油红染色观察细胞形态和脂质堆积情况。用高分辨液相色谱—质谱(UPLC-QTOF/MS)对大鼠肝组织进行代谢组学检测，并利用KEGG数据库分析代谢通路。采用网络药理学对香蜂草苷与NAFLD共同作用的靶点进行预测，并联合代谢组学进一步分析潜在的靶点。结果:香蜂草苷明显减轻大鼠肝损伤、抑制肝脏脂质的过度沉积;正交偏最小二乘判别分析(OPLS-DA)分析显示组间的代谢物有显著差异，火山图显示正常组与模型组存在404个差异代谢物(上调293个，下调111个)，模型组与香蜂草苷组存在147个差异代谢物(上调95个，下调52个);代谢通路分析显示差异代谢物主要富集于鞘脂代谢通路;网络药理学筛选药物与疾病共同靶点共139个，联合代谢组学和网络药理学分析显示，香蜂草苷可通过调节TNF、Bcl2、Mapk8、Pik3ca、Akt1、mTOR、Gsk3β来调控鞘脂代谢通路和胰岛素抵抗。结论:香蜂草苷能够通过鞘脂代谢通路和胰岛素抵抗调节脂质代谢紊乱从而发挥治疗NAFLD的作用。
The mechanism of didymin in alleviating non-alcoholic fatty liver disease in rats analyzed by the integrative analysis of untargeted metabolomics and network pharmacology
Objective:To investigate the mechanism of didymin in alleviating lipid metabolism in non-alcoholic fatty liver disease(NAFLD)using integrative analysis of untargeted metabolomics and network pharmacology.Methods:The rats were randomly divided into normal group,model group and didymin group.The model group and didymin group were fed with a high-fat diet(HFD)for 8 weeks to induce NAFLD animal model,followed by the corresponding administration for further 8 weeks.Hematoxylin-eosin(HE)and Oil Red O staining were used to observe the cell morphology and lipid accumulation.Metabolomics of rat liver tissue was examined with high-resolution liquid chromatography-mass spectrometry(UPLC-QTOF/MS),and metabolism pathway was analyzed using Kyoto Encyclopedia of Genes and Genomes(KEGG)database.The overlapping target genes between didy-min and NAFLD were predicted by network pharmacology analysis,and the potential targets were further ana-lyzed by the integrative analysis of metabolomics and network pharmacology.Results:Didymin significantly re-duced liver injury and inhibited excessive lipid deposition in rats.Orthogonal partial least squares discriminant analysis(OPLS-DA)showed that significant differences in the metabolites between groups.The volcano plots in-dicated 404 differential metabolites between the normal group and the model group(293 up-regulated and 111 down-regulated),and 147 between the model group and the didymin group(95 up-regulated and 52 down-regulat-ed);metabolic pathway analysis showed that the differential metabolites were mainly enriched in the sphingolipid metabolism pathway.Network pharmacology analysis suggested that there was a total of 139 drug-disease com-mon targets,and further integrative analysis indicated that didymin could regulate the sphingolipid metabolism pathway and insulin resistance by affecting the target genes TNF,Bcl2,Mapk8,Pik3ca,Akt1,mTOR,Gsk3β,re-spectively.Conclusion:Didymin can regulate lipid metabolism disorder through the pathway of sphingolipid me-tabolism and insulin resistance,ultimately playing a role in the treatment of NAFLD.

didyminnon-alcoholic fatty liver diseasemetabolomicsnetwork pharmacologyhigh-resolution liquid chromatography-mass spectrometrysphingolipid metabolism pathwayinsulin resistance

莫柔、方斌、林兴、黄权芳、黄仁彬

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广西医科大学,南宁 530021

广西中医药大学第一附属医院药学部,南宁 530023

香蜂草苷 非酒精性脂肪肝 代谢组学 网络药理学 高分辨液相色谱—质谱 鞘脂代谢通路 胰岛素抵抗

国家自然科学基金资助项目

82060755

2024

10.16190/j.cnki.45-1211/r.2024.06.012

广西医科大学学报
广西医科大学

广西医科大学学报

CSTPCD
影响因子：0.788
ISSN：1005-930X
年,卷(期)：2024.41(6)