多氯联苯与高脂联合暴露SD大鼠的代谢组学研究  

Metabonomics analysis of effects induced by PCBs and high fat diet combined exposure in SD rats

作　　者：李致远[1,2] 王以美[2] 薛耀明[1] 方毅[3] 颜贤忠[4] 贾栗[2] 张廷芬[2] 华辰凤 张琪[4] 彭双清[2] 

机构地区：[1]南方医科大学南方医院,广州510515 [2]军事医学科学院疾病预防控制所,北京100071 [3]军事医学科学院附属医院,北京100071 [4]军事医学科学院国家生物医学分析中心,北京100850

出　　处：《军事医学》2015年第4期266-270,301,共6页Military Medical Sciences

基　　金：国家重点基础研究发展计划资助项目(2011CB503803)

摘　　要：目的分析多氯联苯(PCBs)与高脂饮食暴露后SD大鼠尿液代谢组变化,探讨PCBs对糖、脂肪等代谢的影响及可能的毒性机制,并寻找潜在的候选生物标志物。方法雄性SD大鼠随机分为对照组、高脂组、PCBs组、PCBs与高脂联合暴露组。于染毒6周收集尿液样本,采集尿液的1H NMR谱,采用主成分分析法(PCA)分析数据。结果 PCA得分图显示,联合暴露组与其他3组可完全区分,表明该组动物尿液代谢特征与其他3组存在较大差异。PCA载荷图显示,联合暴露组大鼠尿液中乳酸、葡萄糖、肌酸、2-羟异戊酸含量显著上升;柠檬酸、琥珀酸、牛磺酸、马尿酸、氧化三甲胺(TMAO)含量显著下降。结论 PCBs与高脂联合暴露导致大鼠尿液中三羧酸循环的中间产物含量降低或与能量代谢相关的代谢物蓄积,可能与线粒体功能受损、能量代谢障碍有关。这些效应可能会进一步导致糖类、脂肪、氨基酸等营养物质代谢紊乱。含量发生显著变化的代谢物可能成为PCBs与高脂饮食暴露的候选毒性标志物。Objective To explore the effect on metabolism of glucose and lipids, potential toxicity mechanism and possible biomarker candidates by analyzing urine metabonome changes of rats after oral administration of polychlorinated biphenyl congeners（PCBs）and high fat diet alone or in combination. Methods Male SD rats were divided randomly into control group,high fat diet group, PCBs group and combination group of PCBs and high fat diet. Urine samples were collected after 6-week treatment, I H NMR spectra were performed and analyzed by principal component analysis （PCA）. Results The PCA scores plot of urine 1 H NMR data showed that the combined group could be easily distinguished from the other three groups, suggesting great difference in metabolism. The loading plot of the PCA revealed significant increase in the levels of lactate, glucose, creatine, 2-hydroxy-isovaleric acid and reduction in the levels of citrate, succinate, taurine, hippurate and trimethylamine oxide （TMAO） in the combined exposure group after six-week exposure. Conclusion The altered levels of metabolites induced by combined exposure of PCBs and high fat diet may be related to the injury to mitochondrial function, reduction of energy metabolism in tricarboxylic acid cycle （TAC）. These effects possibly lead to perturbations in the metabolism of glucose, lipid and amino acids. The altered metabolites may be considered biomarker candidates of toxicity induced by exposure to PCBs and high fat diet.

关 键 词：多氯联苯 高脂饮食 2型糖尿病 代谢组学 主成分分析 

分 类 号：R114[医药卫生—卫生毒理学]