基于代谢组学探讨丹膝颗粒治疗大脑中动脉闭塞大鼠的作用机制*
作者:龙慧玲1,唐 伟2,陶新如3,冯小龙3,杨智巍4,蔡 媛3,李鹏辉3,彭艳梅3
单位:1.湖南省药品审评与不良反应监测中心,湖南 长沙 410013; 2.湖南省中医药研究院附属医院,湖南 长沙 410013; 3.湖南省中医药研究院,湖南 长沙 410013; 4.湘南学院,湖南 郴州 423099
引用:引用:龙慧玲,唐伟,陶新如,冯小龙,杨智巍,蔡媛,李鹏辉,彭艳梅.基于代谢组学探讨丹膝颗粒治疗大脑中动脉闭塞大鼠的作用机制[J].中医药导报,2025,31(6):61-66.
DOI:10.13862/j.cn43-1446/r.2025.06.011
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摘要:目的:基于代谢组学探讨丹膝颗粒(DXKL)治疗大脑中动脉闭塞(MCAO)大鼠的作用机制。方法:使用改良线栓法建立MCAO大鼠模型,根据神经性神经功能评估丹膝颗粒对MCAO大鼠的治疗效果,并通过液质联用技术检测大鼠缺血侧脑组织代谢物的变化。结果:造模成功后,丹膝颗粒给药组能显著降低MCAO大鼠的神经功能评分(P<0.01),代谢组学结果显示,MCAO-Sham组有12种差异代谢物,其中7个化合物上调,5个代谢物下调;MCAO-DXKL组中有38种差异代谢物,其中22个化合物上调,16个下调;共有差异代谢物为L-天冬氨酸;丹膝颗粒治疗后能显著回调L-天冬氨酸发生紊乱的代谢物水平。MCAO-DXKL组中38种差异代谢物结合差异代谢物L-天冬氨酸的KEGG通路富集结果分析,推测丹膝颗粒治疗缺血性脑卒中的作用机制可能与D-氨基酸代谢,半胱氨酸和蛋氨酸代谢过程,以及甘氨酸、丝氨酸和苏氨酸代谢过程有关。结论:丹膝颗粒能够改善MCAO大鼠偏瘫的症状,显著降低神经功能评分,其机制可能与D-氨基酸代谢,半胱氨酸和蛋氨酸代谢过程,以及甘氨酸、丝氨酸和苏氨酸代谢过程有关。
关键词:脑卒中;丹膝颗粒;脑组织;代谢组学;大鼠
Abstract:
Objective: To explore the mechanism of action of Danxi granule (DXKL) in treating middle cerebral artery occlusion (MCAO) rats based on metabolomics. Methods: The MCAO rat model was established by the modified thread embolization method. The therapeutic effect of DXKL on MCAO rats was evaluated according to the neurological function score. The changes of metabolites in rat brain tissue were detected by liquid chromatography-mass spectrometry. Results: After successful modeling, the administration group of DXKL could significantly reduce the neurological function score of MCAO rats (P<0.01). The metabolomics results showed that there were 12 differential metabolites in the MCAO-Sham group, among which 7 compounds were up-regulated and 5 metabolites were down-regulated. There were 38 differential metabolites in the MCAO-DXKL group, among which 22 compounds were up-regulated and 16 were down-regulated. The common differential metabolite was L-aspartic acid. After treatment with DXKL, the metabolite level of L-aspartic acid with disordered metabolism could be significantly adjusted back. Based on the KEGG pathway enrichment results analysis of 38 differential metabolites in the MCAO-DXKL group combined with the differential metabolite L-aspartic acid, it was speculated that the mechanism of action of DXKL in treating ischemic stroke might be related to D-amino acid metabolism, cysteine and methionine metabolism processes, and glycine, serine and threonine metabolism processes. Conclusion: Danxi granule can improve the symptoms of hemiplegia in MCAO rats, and reduce the neurological function score significantly. The mechanism may be related to D-amino acid metabolism, cysteine and methionine metabolism processes, and glycine, serine and threonine metabolism processes.
Key words:stroke; Danxi granule; brain tissue; metabolomics; rat
发布时间:2026-01-03
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