基于代谢组学分析香蜂草苷抗非酒精性脂肪肝病的作用机制  

Research on mechanism of anti-nonalcoholic fatty liver disease by didymin based on metabolomics

作　　者：方斌 莫柔 黄仁彬[1] 黄权芳[2] FANG Bin;MO Rou;HUANG Renbin;HUANG Quanfang(Guangxi Medical University,Nanning 530021,China;Pharmaceutical Department,the First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530023,China)

机构地区：[1]广西医科大学,南宁530021 [2]广西中医药大学第一附属医院药学部,南宁530023

出　　处：《广西医科大学学报》2024年第8期1111-1119,共9页Journal of Guangxi Medical University

基　　金：国家自然科学基金资助项目(No.82060755)。

摘　　要：目的:基于非靶向代谢组学和生物信息学方法研究香蜂草苷抗非酒精性脂肪肝病(NAFLD)的作用机制。方法:将18只雄性SD大鼠随机分为正常对照组、模型组和香蜂草苷组(3 mg/kg),每组6只。使用高脂饲料喂养8周诱导建立NAFLD大鼠模型。香蜂草苷组每天灌胃给予香蜂草苷治疗8周,正常对照组和模型组灌胃给予等量生理盐水。采用苏木精—伊红(HE)染色和油红O染色观察各组大鼠肝组织病理学变化。使用超高效液相—质谱(UPLC-Xevo G2-XS QTof)检测大鼠肝匀浆代谢物,以P<0.05和变化倍数(|FC|)>2为标准筛选差异代谢物,进行代谢物分类富集分析;以总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、游离脂肪酸(FFA)和胰岛素抵抗(IR)等NAFLD相关指标为疾病表型,构建加权代谢共表达网络分析(WMCNA),筛选出与NAFLD相关的核心代谢物。取差异代谢物和核心代谢物交集进行生物标志物分析。结果:与模型组比较,香蜂草苷组大鼠体重降低,肝脏脂质沉积减少,肝脏病理损伤减轻。代谢组学结果表明,共筛选出差异代谢物126个,其中上调50个,下调76个(香蜂草苷组vs.模型组)。WMCNA筛选出核心代谢物189个,主要为磺酸及其衍生物、脂肪酸化合物。取差异代谢物和核心代谢物交集在Metaboanlyst在线数据库分析可得25个潜在生物标志物,其中脂酰类化合物Isopropylmalic acid(P<0.05,FC=-2.81)和脂肪酸生成相关化合物Alpha-Linoleoylcholine(P<0.05,FC=-1.39)、3-trans,5-cis-Octadienoyl-CoA(P<0.05,FC=-1.78)变化差异具有统计学意义。结论:香蜂草苷可能通过调节Isopropylmalic acid、Alpha-Linoleoylcholine和3-trans,5-cis-Octadienoyl-CoA的代谢水平,起到改善NAFLD的作用,为缓解脂质代谢紊乱提供前期实验基础。Objective:To study the mechanism of anti-nonalcoholic fatty liver disease(NAFLD)by didymin based on non-targeted metabolomics and bioinformatics methods.Methods:Eighteen male SD rats were random-ly divided into normal group,model group,and didymin group(3 mg/kg),with 6 rats in each group.NAFLD rat model was induced by feeding high-fat diet for 8 weeks.The didymin group was given vanillin every day for 8 weeks,and the normal group and model group were given the same amount of normal saline.Hematoxylin-eosin(HE)staining and Oil Red O staining were used to observe the histopathological changes of liver in each group.The metabolites of rat liver homogenate were detected by ultra-high-performance liquid-mass spectrometry(UPLC-Xevo G2-XS QTof).The differential metabolites were screened based on criteria of P<0.05 and the change ratio(|FC|)>2),and the metabolites were classified and enriched.Using total cholesterol(TC),triglycer-ide(TG),low density lipoprotein(LDL),high density lipoprotein(HDL),free fatty acid(FFA),insulin resistance(IRI)and other NAFLD-related indicators as disease phenotypes,weighted metabolites correlation network analy-sis(WMCNA)was built and the hub metabolites associated with NAFLD were screened.The intersection of dif-ferential metabolites and hub metabolites was analyzed for biomarkers.Results:Compared with the model group,the didymin group could reduce body weight,liver lipid deposition and liver damage in rats.Metabolo-mics results showed that 126 differential metabolites were selected,of which 50 were up-regulated and 76 were down-regulated(didymin group vs.model group).WMCNA screened 189 hub metabolites,mainly sulfonic acid and its derivatives,fatty acyl compounds,and 25 potential biomarkers were obtained by the intersection of the dif-ferential metabolites and hub metabolites in Metaboanlyst dataset.Among them,the differences in the fatty acyl compound Isopropylmalic acid(P<0.05,FC=-2.81)and the fatty acid-related compounds Alpha-Linoleoylcho-line(P<0.05,FC=-1.39)and 3-trans,5-cis-Octadieno

关 键 词：香蜂草苷 非酒精性脂肪肝病 代谢组学 加权代谢物共表达网络分析 

分 类 号：R285.5[医药卫生—中药学]