急性肝衰竭大鼠血清差异性代谢物的代谢组学分析

Metabonomics analysis on serum metabolites from rats with acute hepatic failure

目的:以正常大鼠为参照,探索急性肝衰竭(AHF)大鼠血清中的差异性代谢物。方法:采用腹腔注射脂多糖(LPS)和D-氨基半乳糖胺(D-GaIN)建立AHF大鼠模型。收集30只AHF和30只正常大鼠的血清样本,采用气相色谱-质谱联用(GC/MS)的代谢组学方法对样本进行检测,并采用主成分分析(PCA)和偏最小二乘法-判别分析(PLS-DA)方法进行建模分析,结合t检验进行组间比较,最终确定AHF大鼠血清代谢物谱中特异性的代谢物。结果:在AHF组大鼠血清中有11个主要代谢物与正常大鼠血清比较差异有统计学意义(P<0.05),包括甘氨胆酸、甘氨鹅脱氧胆酸、牛磺鹅脱氧胆酸、甘氨酸、海藻糖、十六烷酸酰胺、卵磷脂、油酸酰胺、硬脂酰胺、甘露糖、硬脂酸。结论:与正常大鼠比较,AHF组大鼠血清中存在差异性代谢物,这些代谢物可能作为AHF特异性生物标志物,并有助于揭示AHF的发病机制。

Objective： To investigate the different metabolites in the serum of rats with acute hepatic failure （AHF） compared with those in normal rats. Methods： The AHF rat model was established through intraperitoneal injection of lipopolysacchride （LPS） and D-amino galactosamine （D-GaIN）. Serum samples from 30 on AHF rats and 30 normal rats were collected and subsequently detected by metabonomics method based gas chromatography mass spectrometry （GC/MS）. Principal components analysis （PCA） and partial least squares-discriminate analysis （PLS-DA） were utilized for data analysis. Spec fic different metabolites of serum in AHF rats were finally confirmed by combining with unidimensional t test. Results： There were 11 metabolites in the serum of AHF rats that were different from normal rats, including glycocholic acid, glycochenodeoxycholic acid, taurochenodeoxycholic acid, glycine, mycose, hexadecanoic acid amide, lecithin, oleamide, stearamide, mannose and stearic acid. Conclusion： Compared with normal rats, there were different metabolites identified in the serum of rats with AHF, which could be used as specific biomarkers of AHF and might help to clarify the underlying mechanism of pathogenesis of AHF.