蟾酥急性毒性的代谢组学研究

Metabonomics Study on the Acute Toxicity of Toad Venom

运用代谢组学方法结合心电图分析对蟾酥导致的大鼠急性毒性进行了研究,通过超高效液相色谱-飞行时间质谱建立了大鼠血清的代谢指纹谱,采用主成分分析和正交偏最小二乘判别分析法分析了对照组和各给药组之间的代谢物谱差异,通过变量重要性投影和t检验选取潜在的生物标志物,结合质谱同位素分析、数据库检索以及标准品对照法对潜在生物标志物进行了鉴定.结果表明,蟾酥可导致大鼠心脏心率减慢、心律失常、甚至出现心肌梗塞现象,其导致心脏损伤的途径可能是通过阻碍自由脂肪酸再酰化或激活蛋白激酶通路干扰了脂质代谢,该结果为阐述蟾酥毒性作用机理提供了新思路.

The metabonomics method coupled with electrocardiogram were applied to the study on the acute toxicity of toad venom.The profiles of serum samples were obtained with ultra performance liquid chromatography coupled with time-of-flight mass spectrometry（UPLC/TOF-MS）.The data were firstly processed with the software Markerlynx and then analyzed with the principal components analysis（PCA） and orthogonal partial least squares discriminate analysis（OPLS-DA）.The potential biomarkers were screened out according to the VIP（variable importance in projection） value and identified with t-fit,database and corresponding reference standards.The metabolites of significant intergroup differences were finally found to be li-pids related to myocardial energy metabolism.According to the biological functions of the obtained potential biomarkers,it was deduced that the heart injury may be induced by disturbing lipid metabolism through hampering the re-acylation of free fatty acid or activating protein kinase pathway.This study provides a new approach to discover the underlying mechanism of toad venom toxicity.