硫代乙酰胺诱导肝损伤大鼠的血清脂肪酸代谢轮廓的研究

The Metabolic Profiling of Serum Fatty Acids in Thioacetamide-induced Liver Injured Rats

基于气相-质谱联用技术测定硫代乙酰胺(TAA)组和对照组的大鼠血清中16种脂肪酸的含量,结合主成分分析(PCA)和偏最小二乘法-判别分析(PLS-DA)分析腹腔注射TAA后大鼠的血清游离和酯化脂肪酸代谢轮廓的变化及发现潜在生物标志物。含量测定结果表明,TAA组的大鼠血清中9种游离脂肪酸和2种酯化脂肪酸的水平显著升高,3种游离脂肪酸和5种酯化脂肪酸的水平显著降低。PCA分析表明腹腔注射TAA后大鼠血清脂肪酸代谢轮廓偏离正常水平,PLS-DA结果表明花生四烯酸、亚油酸、棕榈酸、油酸对表征TAA诱导大鼠肝损伤具有重要贡献,且这四种脂肪酸与临床上诊断肝损伤常用的血清生化指标具有良好的相关性,可作为评价TAA肝毒性的潜在生物标识物。本研究为肝毒化合物诱导的化学肝损伤的评价提供新的方法。

A gas chromatography-mass spectrometry(GC-MS)method was applied to determine the serum concentration of 16 fatty acids in control and thioacetamide(TAA)-treated rats.Furthermore,the change of serum free and esterified fatty acid metabolic profile and potential biomarkers in TAA-caused liver injured rats were analyzed by principal component analysis(PCA)and partial least squares-discriminant analysis(PLS-DA).Concentration results showed that serum levels of 9 free and 2 esterified fatty acids obviously increased as well as that of 3 free and 5 esterified fatty acids significantly decreased in TAA-treated rats when compared with control rats.PCA results illustrated that the metabolic profile of serum fatty acids in TAA-treated rats exhibited obvious difference from the normal level.More importantly,PLS-DA results illustrated that arachidonic acid,linoleic acid,palmitic acid and oleic acid had outstanding contribution on liver injury induced by TAA.The four free fatty acids had good correlation with serum biochemical indicators commonly used in clinical diagnosis of liver injury.Therefore,these species were identified as potential biomarkers of TAA-induced liver injury.The project can provide a new method for evaluating chemical liver injury induced by hepatotoxic compounds.