肝豆灵对铜负荷致肝损伤大鼠肝脏代谢产物的影响

目的 从代谢组学角度探讨肝豆灵对铜负荷大鼠肝损伤的干预机制。 方法 将21只大鼠随机分为正常组、模型组和肝豆灵组，每组7只。正常组大鼠接受普通饲料喂养，其余两组大鼠均接受高铜饲料喂养以复制铜负荷模型，共计12周。从第7周开始，肝豆灵组以肝豆灵灌胃，正常组和模型组予以等容量生理盐水灌胃，直至模型复制结束。以超高效液相色谱/四级杆-飞行时间质谱技术，结合主成分分析和偏最小二乘判别分析方法分析大鼠肝组织代谢物的变化。结果 模型组中溶血磷脂酰胆碱、油酸酰胺含量降低，色氨酸、苯丙氨酸、硬脂酰胺、牛磺酸鹅脱氧胆酸、甘氨胆酸、牛磺胆酸含量升高。肝豆灵组溶血磷脂酰胆碱、油酸酰胺含量升高，色氨酸、苯丙氨酸、硬脂酰胺、牛磺酸鹅脱氧胆酸、甘氨胆酸、牛磺胆酸的含量降低。〖JP〗 结论 肝豆灵对铜负荷大鼠肝损伤具有一定的干预作用，其机制可能与调节胆汁酸代谢、氨基酸代谢、脂代谢途径有关。

Influence of Gandouling on Liver Metabolites in Rats with Liver Injury Induced by Copper Overload

Objective To investigate the mechanism of action of Gandouling in treating liver injury induced by copper overload in rats from the perspective of metabolomics. Methods A total of 21 rats were randomly divided into normal group, model group, and Gandouling group, with 7 rats in each group. The rats in the normal group received normal diets, and those in the other two groups received high-copper diets to establish the model of copper overload; all the rats were fed for 12 weeks. From the 7th week to the end of model establishment, the rats in the Gandouling group were given Gandouling by gavage, and the rats in the other two groups were given the same volume of normal saline by gavage. Ultra-performance liquid chromatography and quadrupole-time-of-flight mass spectrometry, as well as principal component analysis and partial least squares discriminant analysis, were applied to analyze the changes in liver metabolites in rats. Results In the model group, the levels of lysophosphatidylcholine and oleamide decreased, and the levels of tryptophan, phenylalanine, stearamide, taurochenodeoxycholic acid, glycocholic acid, and taurocholic acid increased. In the Gandouling group, the levels of lysophosphatidylcholine and oleamide increased, and the levels of tryptophan, phenylalanine, stearamide, taurochenodeoxycholic acid, glycocholic acid, and taurocholic acid decreased. Conclusion Gandouling has a certain therapeutic effect on liver injury induced by copper overload in rats, and its mechanism of action may be related to regulation of bile acid metabolism, amino acid metabolism, and lipid metabolism.