基于代谢组学分析碱性成纤维细胞生长因子对糖尿病小鼠肝损伤的作用  

The effect of basic fibroblast growth factor on liver injury in diabetic mice:A metabonomics analysis

作　　者：于雯飘 舒琦 魏婷婷 YU Wenpiao;SHU Qi;WEI Tingting(The First School of Medicine,School of Information and Engineering,Wenzhou Medical University,Wenzhou 325035,China;Department of Pharmacy,Zhejiang Cancer Hospital,Hangzhou 310022,China;Laboratory Animal Research Center,Wenzhou Medical University,Whenzou 325035,China)

机构地区：[1]温州医科大学第一临床医学院(信息与工程学院),浙江温州325035 [2]浙江省肿瘤医院药剂科,浙江杭州310022 [3]温州医科大学实验动物中心,浙江温州325035

出　　处：《温州医科大学学报》2023年第6期458-464,共7页Journal of Wenzhou Medical University

基　　金：国家自然科学基金项目(81600653);温州市基础性科研项目(Y20220911)。

摘　　要：目的:基于1H NMR的代谢组学方法探究碱性成纤维细胞生长因子(bFGF)在糖尿病肝损伤中的代谢调控作用。方法:将C57BL/6J小鼠设为wt组,db/db小鼠分为糖尿病肝损伤组(db/db组)和bFGF给药组(b FGF组)。给药10周后处死,收集肝脏组织,一部分做HE染色观察肝组织形态,另一部分采集1H NMR谱,采用偏最小二乘判别分析(PLS-DA)比较3组小鼠肝脏的代谢模式变化以及差异代谢物水平。结果:HE染色结果表明,wt组小鼠肝小叶和肝窦结构清晰,db/db组小鼠肝细胞脂肪变性明显,bFGF干预后,bFGF组脂滴和炎性细胞明显减少,细胞坏死损伤减轻。PLS-DA结果表明,3组小鼠肝脏的代谢模式存在明显差异。代谢物定量分析结果显示,db/db组小鼠肝脏中亮氨酸、异亮氨酸、缬氨酸、乳酸、琥珀酸、肌酐、甘氨酸、三磷酸鸟苷和苯丙氨酸的代谢水平较wt组显著降低,但给予bFGF治疗后其代谢水平显著增加,差异均有统计学意义(P<0.05)。结论:b FGF可以改善糖尿病肝损伤肝脏组织的代谢紊乱,主要涉及到能量代谢、氨基酸代谢和核苷酸代谢。Objective:To observe the effect of basic fibroblast growth factor(bFGF)on diabetic liver injury through remodeling metabolism by 1H nuclear magnetic resonance(1H NMR)-based metabonomics.Methods:C57BL/6J mice acted as control group(wt group).The db/db mice were randomly divided into diabetic liver injury group(db/db group)and bFGF-treated group(bFGF group).The liver tissues were collected from mice after 10 weeks of bFGF treatment.Morphology of liver tissue was examined by hematoxylin-eosin(HE)staining.The characteristic alterations in liver metabolites were explored by the projection to latent structure discriminant analysis(PLS-DA)based on the 1H NMR spectra.Results:HE staining results showed that the structure of hepatic lobules and hepatic sinuses in wt group was clear,and the steatosis of hepatic cells in db/db group was obvious.After bFGF intervention,lipid droplets and inflammatory cells in bFGF group were significantly reduced,and cell necrosis damage was relieved.PLS-DA results showed that there was significant difference in the metabolic profile of liver among the three groups of mice.Quantitative analysis of metabolites showed that,compared with age-matched wt group mice,the levels of leucine,isoleucine,valine,lactate,succinate,creatinine,glycine,guanosine triphosphate and phenylalanine were significantly lower in db/db group mice but they were significantly increased after bFGF treatment(P<0.05).Conclusion:The effect of bFGF on diabetic liver injury could be mediated by remodeling metabolic phenotype,mainly involving energy metabolism,amino acid metabolism and nucleotide metabolism.

关 键 词：糖尿病肝损伤 碱性成纤维细胞生长因子 代谢组学 DB/DB小鼠 

分 类 号：R575[医药卫生—消化系统]