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基于 1H-NMR 的代谢组学研究:中西药物干预对载铜 Wilson 病大鼠纹状体损伤的影响。

H NMR-based metabolomic study of striatal injury in rats with copper-loaded Wilson's disease by Chinese and Western medicine intervention.

机构信息

The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China.

The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China.

出版信息

J Pharm Biomed Anal. 2023 May 30;229:115355. doi: 10.1016/j.jpba.2023.115355. Epub 2023 Mar 25.

DOI:10.1016/j.jpba.2023.115355
PMID:37018958
Abstract

OBJECTIVE

To investigate the metabolic mechanisms of Chinese and Western medicines on the metabolic network of striatal injury in a copper-loaded rat model of Wilson disease (WD) from a metabolomic perspective.

METHODS

We divided 60 rats into 4 groups of 15 rats each according to a random number table, namely the control group, the model group, the Bushen Huoxue Huazhuo Recipe group, and the penicillamine group, and subsequently replicated the WD copper-loaded rat model according to the literature method for a total of 12 weeks. From the 7th week onwards, each intervention group was given an equivalent dose of the corresponding drug, and the control and model groups were given an equal volume of saline gavage until the end of the model replication. We used H NMR metabolomics techniques combined with multivariate statistical methods to describe the changes in the striatal metabolic profile of nerve injury in Wilson's disease and to analyze the effect of different treatments on their biomarker interventions.

RESULTS

Nerve cell damage was evident in the WD copper-loaded rat model and could be reduced to varying degrees by different methods of intervention in the striatal nerve cells. The content of glycine, serine metabolism, and valine metabolism decreased in WD copper-loaded rat model; aspartate content increased after penicillamine intervention; glycolytic metabolism, valine metabolism, taurine metabolism, and tyrosine metabolism increased in the group of Bushen Huoxue Huazhuo Recipe.

CONCLUSION

Different intervention methods of Chinese and Western medicine affect aspartate, glycolysis, taurine, tyrosine, valine, and carbon metabolism in striatal tissues of WD copper-loaded rats, and can regulate the metabolism of small molecules, which in turn have certain repairing effects on nerve damage in WD copper-loaded rats.

摘要

目的

从代谢组学角度探讨中西药物对肝豆状核变性(WD)铜负荷大鼠纹状体损伤代谢网络的代谢机制。

方法

将 60 只大鼠按随机数字表法分为 5 组,每组 12 只,分别为对照组、模型组、补肾活血化浊方组、青霉胺组,随后采用文献方法复制 WD 铜负荷大鼠模型,共 12 周。从第 7 周开始,各干预组给予相应等效剂量药物,对照组和模型组给予等容量生理盐水灌胃,直至模型复制结束。采用 H NMR 代谢组学技术结合多元统计方法描述 WD 铜负荷大鼠纹状体神经损伤的代谢谱变化,并分析不同治疗方法对其生物标志物干预的影响。

结果

WD 铜负荷大鼠模型出现神经细胞损伤,不同方法干预可使纹状体内神经细胞损伤程度不同程度减轻。WD 铜负荷大鼠模型中甘氨酸、丝氨酸代谢和缬氨酸代谢含量降低,青霉胺干预后天冬氨酸含量增加,补肾活血化浊方组糖酵解代谢、缬氨酸代谢、牛磺酸代谢和酪氨酸代谢增加。

结论

中西药不同干预方法影响 WD 铜负荷大鼠纹状体内天冬氨酸、糖酵解、牛磺酸、酪氨酸、缬氨酸和碳代谢,能调节小分子代谢,对 WD 铜负荷大鼠神经损伤有一定修复作用。

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