高氧导致小鼠肠代谢紊乱

Hyperoxia caused intestinal metabolism disorder in mice

目的探讨高氧对小鼠肠道代谢组的影响.方法将16只8周龄雄性C57BL/6小鼠按随机数字表法分为高氧组和对照组,每组8只.高氧组暴露在80%O_(2)中14d;对照组在室内空气中条件饲养14 d.将小鼠麻醉并安乐死,收集盲肠内容物,通过液相色谱-质谱(LC-MS)联合检测进行非靶向代谢组学分析.采用正交偏最小二乘判别分析(OPLS-DA)、火山图分析、热图分析及京都基因和基因组百科全书(KEGG)分析高氧对代谢的影响.结果①OPLS-DA分析显示,R2Y为0.967,Q2为0.796,表示该模型为可靠模型.②火山图及热图分析显示,两组中代谢物表达水平差异具有统计学意义,其中上调代谢物541个,下调代谢物64个,907个无差异,而升高的5-羟基-L-赖氨酸是高氧诱导的最显著的差异代谢物.③KEGG通路富集分析表明,卟啉和叶绿素代谢(P=0.005)、赖氨酸降解(P=0.047)及芳香族化合物降解(P=0.024)是受高氧影响的靶点.④通过KEGG富集代谢途径对代谢产物进行差异分析显示,高氧对卟啉和叶绿素、赖氨酸以及苯、邻甲酚等芳香族化合物的代谢具有显著影响.结论高氧显著诱导了小鼠肠道代谢紊乱,其增强了卟啉和叶绿素的代谢,抑制了赖氨酸的降解,并延缓了苯、邻甲酚等芳香族化合物的降解.

Objective To investigate the effect of hyperoxia on intestinal metabolomics in mice.Methods Sixteen 8-week-old male C57BL/6 mice were randomly divided into hyperoxia group and control group,with 8 mice in each group.The hyperoxia group was exposed to 80%oxygen for 14 days.Mice were anesthetized and euthanized,and cecal contents were collected for untargeted metabolomics analysis by liquid chromatography-mass spectrometry(LC-MS)combined detection.Orthogonal partial least square discriminant analysis(OPLS-DA),volcano plot analysis,heat map analysis,and Kyoto Encyclopedia of Genes and Genomes(KEGG)were used to analyze the effects of hyperoxia on metabolism.Results①OPLS-DA analysis showed that R2Y was 0.967 and Q2 was 0.796,indicating that the model was reliable.②Volcano plot and heat map analysis showed significant statistical differences in the expression levels of metabolites between the two groups,with 541 up-regulated metabolites,64 down-regulated metabolites,and 907 no differences,while the elevated 5-hydroxy-L-lysine was the most significant differential metabolite induced by high oxygen.③KEGG pathway enrichment analysis showed that porphyrin and chlorophyll metabolism(P=0.005),lysine degradation(P=0.047),and aromatic compound degradation(P=0.024)were the targets affected by hyperoxia.④Differential analysis of metabolic products through KEGG enrichment pathway showed that hyperoxia had a significant impact on the metabolism of porphyrin and chlorophyll,lysine,and aromatic compounds such as benzene and o-cresol.Conclusions Hyperoxia significantly induces intestinal metabolic disorders.Hyperoxia enhances the metabolism of porphyrins and chlorophyll,inhibits the degradation of lysine,and delays the degradation of aromatic compounds such as benzene and o-cresol.