基于血清脂肪酸代谢轮廓的化学肝损伤评价研究

Evaluation of Chemical Liver Injury Based on Metabolic Profiling of Serum Fatty Acids

目的从血清脂肪酸代谢轮廓的角度评价四氯化碳(carbon tetrachloride,CCl4)和α-异硫氰酸萘酯(α-naphthalene isothiocyanate,ANIT)诱导的化学肝损伤。方法采用气相-质谱联用技术测定CCl4对照组、CCl4给药组、ANIT对照组和ANIT给药组的大鼠血清中15种游离脂肪酸和酯化脂肪酸的含量,该定量方法的主要参数为毛细管色谱柱DB-225MS、程序升温、电子轰击离子源(70 eV)和选择离子扫描模式(监测m/z 55、67、74、79)。采用偏最小二乘法-判别分析和主成分分析等方法分析大鼠肝损伤后血清脂肪酸代谢轮廓的变化,运用Pearson和典型相关分析方法分析化学肝损伤与脂肪酸代谢的相关性。结果CCl4给药组和ANIT给药组的大鼠血清脂肪酸代谢轮廓明显偏离对照组,且能完全互相区分开;亚油酸、二十二碳六烯酸、油酸、花生四烯酸和硬脂酸对CCl4和ANIT诱导的化学肝损伤具有重要贡献,且这5个游离脂肪酸与丙氨酸氨基转移酶、天冬氨酸氨基转移酶和碱性磷酸酶具有良好的正相关性(P<0.05,P<0.01)。结论血清脂肪酸代谢轮廓与CCl4和ANIT诱导的化学肝损伤密切相关。

OBJECTIVE To evaluate the chemical liver injury induced by carbon tetrachloride(CCl4)andα-naphthalene isothiocyanate(ANIT).METHODS The serum concentrations of 15 kinds of free and esterified fatty acids in rats in CCl4 control group,CCl4 treatment group,ANIT control group and ANIT treatment group were determined by gas chromatography-mass spectrometry.DB-225 MS capillary column was used with programmed temperature increase,and electron impact ion source of 70 eV and selective ion scanning mode(monitoring at m/z 55,67,74,79)were used.The metabolic profiles of serum fatty acids in rats after liver injury were measured by chemometrics such as partial least squares-discriminant analysis and principal component analysis.Pearson and canonical correlation analyses were used to analyze the relationship between chemical liver injury and fatty acid metabolism.RESULTS The metabolic profiles of fatty acids in the serum of CCl4-treated and ANIT-treated rats obviously deviated from those of the control rats,and could be completely distinguished from each other.Linoleic acid,docosahexaenoic acid,oleic acid,arachidonic acid and stearic acid played an important role in the chemical liver injury induced by CCl4 and ANIT.Furthermore,these five free fatty acids were positively correlated with aspartate aminotransferase,alanine aminotransferase and alkaline phosphatase(P<0.05,P<0.01).CONCLUSION The metabolic profile of serum fatty acids is closely related to CCl4-induced and ANIT-induced chemical liver injuries.