环磷酰胺对小鼠免疫抑制作用过程中代谢通路变化的代谢组学研究

目的 采用代谢组学方法，研究环磷酰胺对小鼠免疫抑制作用过程中代谢通路的变化。方法 采用流式细胞术了解免疫细胞变化情况，通过建立偏最小二乘法模型多结果进行判别。以偏最小二乘法模型中变量重要性投影（variable importance in projection，VIP）参数筛选潜在的生物标志物，通过统计分析确定差异性代谢物，借助代谢组学小分子化合物快速鉴定分析软件系统对差异性代谢物进行进一步鉴定分析，通过搜库及运算最终确定差异代谢物质9种，通路富集结果分析差异代谢通路3条。结果 环磷酰胺对正常机体的不饱和脂肪酸的生物合成、线粒体脂肪酸代谢、甘油磷脂代谢、甾类激素的生物合成、花生四烯酸代谢、脂肪酸代谢、嘧啶的生物合成等代谢通路均产生明显影响。结论 环磷酰胺在正常组与实验组中影响最重要的代谢通路为花生四烯酸代谢、甘油磷脂代谢和嘧啶代谢。

Metabolomic analysis of the changes of pathways in immunosuppressive mechanism caused by cyclophosphamide in mice

Objective To investigate the changes of metabolic pathways in the process of immunesuppression in mice caused by cyclophosphamide by metabolomic analysis. Methods Flow cytometry was used to detect the changes of immune cells, and the results were analyzed using partial least squares model. The potential biomarkers were screened by variable importance in projection (VIP) parameters in the partial least squares model, and the differential metabolites were determined by statistical analysis. The differential metabolites were identified using the metabolomics rapid identification and analysis software. Nine kinds of metabolites were identified by searching and calculation, and result of pathway enrichment showed three differential metabolic pathways.Results Cyclophosphamide had a significant effect on the biosynthesis of unsaturated fatty acids, metabolism of mitochondrial fatty acids, metabolism of glycophospholipid, biosynthesis of steroid hormones, metabolism of arachidonic acid, metabolism of fatty acids, and the biosynthesis of pyrimidine.Conclusions The most important metabolic pathways affected by cyclophosphamide in the normal body are the metabolism of arachidonic acid, glycophospholipid and pyrimidine.