代谢组学法分析骨髓抑制模型小鼠血清小分子代谢产物

Analysis on metabolites with small molecule of serum in bone marrow suppression model mice with metabolomics method

骨髓抑制是恶性肿瘤患者化疗后常见的症状,研究骨髓抑制造成体内代谢产物的变化可以为诊断骨髓抑制病症发展状况及采用药物治疗提供思路。采用雄性BalB/C小鼠腹腔注射环磷酰胺建立骨髓抑制模型,通过气相色谱-质谱(GC-MS)对正常与造模小鼠血液代谢产物进行指纹图谱分析,然后采用主成分分析(PCA)和正交偏最小方差判别分析(OPLS-DA)对代谢组学数据进行多维统计分析。与对照组相比,骨髓抑制模型小鼠血浆中潜在的差异表达代谢标志物有15个,其中葡萄糖-1-磷酸、对硝基苯酚、乙酰苯胺、可的松、烟酰胺、马钱苷、咖啡酸、亚油酸和油酸这9种物质的表达差异有统计学意义(P<0.05)。结果表明,代谢产物可作为骨髓抑制研究中的重要标记物,有助于揭示化疗所致骨髓抑制的发病机制,判断疾病发展阶段以及后续治疗手段的有效性。

Bone marrow suppression is a common symptom in patients with malignant tumor afer chemotherapy.Studying the changes of metabolites caused by bone marrow depressioncan provide insights for the diagnosis of bone marrow suppression disease and for the developmentof drug therapy.Male BalB/C mice were injected with cyclophosphamide to establish abone marrow suppression model.Gas chromatography-mass spectrometry(GC-MS)with fingerprinting was used to analyze the normal and model mice blood metabolites.Principal component analysis and orthogonal to partial least squares discriminant analysis(OPLS-D A)onmetabolomics for data multidimensional statistical analysis was also used.Compared to the normalgroup in terms of the metabolic profile of bone marrow suppression mice,there were15endogenous metabolites in mouse plasma,nine of which were statistically significantly different,including glucose-1-phosphate,4-nitrophenol,acetanilide,cortisone,nicotinamide,loganin,caffeic acid,linoleic acid and oleic acid(P<0.05).These results indicate that metabolitecan be used as an important marker in bone marrow suppression,which can help to revealthe pathogenesis of bone marrow suppression induced by chemotherapy and determine thedisease development stage and the effectiveness of follow-up treatment.