大鼠鼠尾振动模型的代谢组学研究
Metabolomics study of rat tail vibration model
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摘要:
背景 手臂振动综合征所涉及的相关代谢物及代谢途径尚未阐明。
目的 通过代谢组学方法研究局部振动对大鼠血清中内源性代谢物的影响，并初步探讨内源性代谢物发挥作用的代谢通路，为进一步研究手臂振动综合征的作用机制提供参考依据。
方法 选取32只7~8周龄的SPF级雄性SD大鼠，平均体重为（211.3±11.1）g，随机分为对照组（Ctrl组，14只）、7 d振动组（9只，连续接振7 d）、14 d振动组（9只，连续接振14 d）。每天振动4 h，振动频率为125 Hz，频率计权加速度为4.9 m·s−2，振动方向为线性垂直振荡，Ctrl组除不接触振动外其他条件与振动组相同。接振完成后，腹主动脉采血取血浆，经代谢组学样品制备处理后，通过超高效液相色谱串联飞行时间质谱联用方法分析大鼠血清代谢组的全局变化。采用主成分分析法（PCA）探究大鼠血清代谢轮廓变化，利用正交偏最小二乘判别分析（OPLS-DA）筛选出差异性代谢物，并结合在线数据库对差异性代谢物进行代谢通路富集分析。
结果 PCA分析显示，与Ctrl组相比，7 d组、14 d组大鼠血清代谢轮廓区分明显；7 d组和14 d组大鼠血清代谢轮廓部分重叠。OPLS-DA分析显示各组间代谢存在差异，解释能力
R 2Y =0.914，预测能力Q 2=0.58。通过OPLS-DA分析从7 d组和14 d组分别筛选出26种和119种差异性代谢物，其中7 d组和14 d组间有24种共同差异性代谢物。代谢组学通路分析结果显示，在14 d组中大鼠血清代谢变化主要与花生四烯酸代谢有关，其中具有显著影响的代谢物为花生四烯酸、前列腺素E2和前列腺素D2。结论 局部振动可影响大鼠体内正常代谢。振动14 d时中具有显著影响的代谢途径为花生四烯酸代谢，花生四烯酸、前列腺素E2、和前列腺素D2为具有显著影响的差异性代谢物。
Abstract:Background The metabolites and metabolic pathways of hand-arm vibration syndrome have not yet been elucidated.
Objective To investigate the effect of local vibration on endogenous metabolites in rat serum by metabolomic analysis, to preliminarily explore the potential metabolic pathway of endogenous metabolites, so as to provide evidence for further research on the mechanism of hand-arm vibration syndrome.
Methods Thirty-two SPF male SD rats, (211.3±11.1) g, 7−8 weeks of age, were selected and randomly divided into three groups: control group (14 rats, without vibration), 7 d vibration group (9 rats, continuously vibration for 7 d), and 14 d vibration group (9 rats, continuous vibration for 14 d). The vibration rats were vibrated every day for 4 h, the frequency weighted acceleration was 4.9 m·s−2, the vibration frequency was 125 Hz, and the vibration direction was one-way vertical vibration. The control group had the same conditions except not contacting vibration. After the vibration exposure, the blood samples taken from the abnormal aorta of rats were collected, and the changes of rat serum metabolome were analyzed by ultra-performance liquid chromatography-tandem time-of-flight mass spectrometry. Principal components analysis (PCA) was used to explore changes in rat serum metabolic profile, and orthogonal partial least squares-discriminant analysis (OPLS-DA) was used to screen out differential metabolites. Combined with online databases, a metabolic pathway enrichment analysis of differential metabolites was performed.
Results The PCA analysis showed that compared with the control group, the rat serum metabolic profiles in the 7 d group and the 14 d group were clearly differentiated, and the rat serum metabolic profiles in the 7 d group and the 14 d group partially overlapped. The OPLS-DA analysis showed significant differences between groups. The main parameters were: model interpretation rate
R 2Y =0.914, model predictive abilityQ 2=0.58. The OPLS-DA analysis screened out 26 and 119 differential metabolites from the 7 d group and the 14 d group respectively, and there were 24 common differential metabolites between the 7 d group and the 14 d group. The metabolomic pathway analysis showed that local vibration-induced changes in rat serum metabolism were mainly related to arachidonic acid metabolism in the 14 d group, among which the metabolites with significant effects were arachidonic acid, prostaglandin E2, and prostaglandin D2.Conclusion Local vibration could affect the normal metabolism in rats, and the metabolic pathway with significant influence is arachidonic acid metabolism after a 14 d exposure and the involved metabolites are arachidonic acid, prostaglandin E2, and prostaglandin D2.
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