基于代谢组学研究经方天麻钩藤饮对抽动障碍模型小鼠的保护作用机制OA

Objective This study aimed to investigate the mechanism of Tianma Gouteng Decoction(天麻钩藤饮)in the treat-ment of tic disorders by examining its intervention effects on tic disorder model mice and its impact on striatal metabolites in brain tissue using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC/Q-TOF MS).Methods Sixty male ICR mice were chosen and randomly allocated into 6 groups with 10 mice in each,specifically the con-trol group,the model group,the western medicine group,as well as the Tianma Gouteng Decoction high,medium and low dose groups.A tic disorder model in mice was constructed via intraperitoneal injection of iminodipropionitrile(IDPN).The therapeutic effect of Tianma Gouteng Decoction on tic disorder model mice was preliminarily evaluated by comprehensively considering chan-ges in mouse behavior,histopathology,as well as the levels of dopamine(DA),5-hydroxytryptamine(5-HT)and norepineph-rine(NE)in the brain tissue of mice.UPLC/Q-TOF MS was used to detect striatal metabolites in the brain tissue of the mice in the control group,the model group,the western medicine group and Tianma Gouteng Decoction high,medium and low dose groups.Orthogonal partial least squares-discriminant analysis was adopted for multivariate statistical analysis and pattern recog-nition,aiming to screen out differential metabolites.Metabolic pathway enrichment was performed using the MetaboAnalyst 5.0 database.Results Tianma Gouteng Decoction could significantly improve the stereotyped behavior scores of tic disorder model mice,reduce the lung index,lower the level of 5-HT and raise the levels of DA and NE.In particular,when compared with those in the control group,the level of 5-HT in the brain tissue of the mice in the model group was significantly higher(P＜0.05),whereas the levels of DA and NE were significantly reduced(P＜0.05).In comparison with the model group,the 5-HT levels in the brain tissue of the mice in the Tianma Gouteng Decoction high,medium and low dose groups were significantly lowered,while the levels of DA and NE were significantly elevated(P＜0.05).Further comparison showed that the content of 5-HT in the brain tissue of the mice in the Tianma Gouteng Decoction high-dose group was lower than that in the Tianma Gouteng Decoc-tion medium and low dose groups,while the contents of DA and NE were higher(P＜0.05).Metabolomics results revealed that there were more than 50 differential metabolites related to the regulation of Tianma Gouteng Decoction,including glycerophospho-lipids,linoleic acid and arachidonic acid.Conclusion From a metabolomics standpoint,this research explored the therapeutic mechanism of Tianma Gouteng Decoction in addressing tic disorders,laying a foundation for research and clinical application of Tianma Gouteng Decoction in the treatment of tic disorders.