【摘要】 目的 利用16S rDNA和代谢组学技术分析笑气中毒小鼠肠道菌群结构及其代谢物的变化，并分析肠道菌群和代谢物之间的相关性，进而探讨肠道微生物与笑气中毒机制的关联性。方法 C57BL/6小鼠被随机分成对照组和笑气中毒组（n=6），将小鼠放置于染毒装置中，中毒组每次给予90 000 ppm笑气，染毒28天，2次/天，每次1 h；对照组给予空气。末次染毒结束24 h后收集小鼠粪便，利用16S rDNA测序技术分析微生物菌群结构差异，筛选显著差异菌群；利用代谢组学技术检测粪便样本中代谢物的变化，寻找差异代谢物，并对得到的肠道差异菌群和差异代谢物进行相关性分析。结果 16S rDNA结果显示，笑气中毒组较对照组肠道菌群的丰富度升高而物种多样性无显著变化，两组之间肠道菌群结构也存在显著差异。代谢组学结果显示共筛选出112种与笑气中毒相关的显著差异代谢物，主要涉及cAMP信号通路和鞘脂代谢2条代谢通路。Spearman相关性分析发现肠道差异菌群与差异代谢物之间存在密切的关联性。结论 笑气中毒后会引起机体肠道菌群结构和代谢物谱改变，且肠道菌群丰度的变化影响多条代谢通路，这可能与笑气中毒会损伤神经系统和血液系统有关，为笑气中毒机制的进一步研究和临床治疗提供依据。更多还原

【Abstract】 Objective To analyze changes in intestinal microbiota composition and metabolites in mice with nitrous oxide poisoning using 16S rDNA sequencing and metabolomics, and to examine correlations between gut microbes and metabolites in order to explore the mechanisms of nitrous oxide poisoning. Methods C57BL/6 mice were randomly divided into a control group and a nitrous oxide poisoning group(n = 6). The poisoning group was exposed to 90,000 ppm nitrous oxide twice daily for 1 h over 28 days, while the control group was exposed to air. Fecal samples were collected 24 h after the last exposure. 16S rDNA sequencing was used to analyze structural differences in microbial communities and identify significantly different taxa. Metabolomics analysis was performed to detect changes in fecal metabolites and identify differential metabolites. Correlation analysis was conducted between differential microbiota and metabolites. Results 16S rDNA sequencing showed that the poisoning group had increased microbial abundance compared with controls, while species diversity remained unchanged. Significant differences were observed in gut microbiota structure between groups. Metabolomics identified 112 differential metabolites related to nitrous oxide poisoning, mainly involving the cAMP signaling pathway and sphingolipid metabolism. Spearman correlation analysis revealed a strong association between differential microbiota and differential metabolites. Conclusion Nitrous oxide poisoning alters the structure and metabolic profiles of intestinal microbiota. Changes in microbial abundance affect multiple metabolic pathways, which may be related to damage to the nervous and hematological systems. These findings provide a basis for further research on the mechanisms of nitrous oxide poisoning and for clinical treatment.更多还原