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为探讨阿霉素致大鼠肝毒性的作用机制,本研究采用1H NMR代谢组学技术对大鼠肝脏内源代谢物变化进行研究。通过多元统计分析,鉴定了16个与阿霉素肝毒性密切相关的潜在生物标志物。进一步通过代谢通路分析(Met PA),发现阿霉素显著影响肝脏苯丙氨酸、酪氨酸和色氨酸生物合成,缬氨酸、亮氨酸和异亮氨酸生物合成,苯丙氨酸代谢,甘氨酸、丝氨酸和苏氨酸代谢,丙氨酸、天门冬氨酸和谷氨酸代谢,以及酪氨酸代谢。阿霉素肝脏毒性的发生与干扰氨基酸、脂质、嘌呤代谢、能量代谢、生物转化及氧化应激等过程密切相关。本研究从代谢的角度分析了阿霉素对肝脏代谢的影响,为进一步分析其毒性机制奠定了基础。
In order to explore the mechanism of doxorubicin-induced liver toxicity in rats, 1H NMR metabonomic techniques were used to study the changes of liver endogenous metabolites in rats. By multivariate statistical analysis, 16 potential biomarkers closely related to doxorubicin hepatotoxicity were identified. Further through metabolic pathway analysis (Met PA), doxorubicin was found to significantly affect liver phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis, amphetamine Acid metabolism, glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism, and tyrosine metabolism. Adriamycin liver toxicity occurs with interference with amino acids, lipids, purine metabolism, energy metabolism, biotransformation and oxidative stress and other processes are closely related. In this study, the metabolic effects of doxorubicin on liver metabolism were analyzed, which laid the foundation for further analysis of its toxicity mechanism.