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 1H 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.
CONCLUSIONS: 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.
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 1H 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.
CONCLUSIONS: 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对肝豆病(WD)载铜大鼠纹状体损伤代谢网络的影响。
方法：将60只大鼠按随机数字表法分为4组，每组15只。即对照组，模型组，补肾活血化浊方组,和青霉胺组，随后根据文献方法复制WD载铜大鼠模型共12周。从第七周开始，每个干预组给予等效剂量的相应药物，对照组和模型组给予等量的生理盐水灌胃直至模型复制结束。我们使用1HNMR代谢组学技术结合多变量统计方法来描述Wilson病神经损伤的纹状体代谢谱的变化，并分析不同治疗方法对其生物标志物干预的影响。
结果：在WD载铜大鼠模型中神经细胞损伤明显，通过不同的干预方法对纹状体神经细胞均有不同程度的减轻。甘氨酸的含量，丝氨酸代谢，WD载铜大鼠模型缬氨酸代谢下降；青霉胺干预后天冬氨酸含量增加；糖酵解代谢，缬氨酸代谢，牛磺酸代谢,补肾活血化浊方组酪氨酸代谢增加。
结论：中西医不同干预方法对天冬氨酸,糖酵解,牛磺酸,酪氨酸,缬氨酸,WD载铜大鼠纹状体组织中的碳代谢，可以调节小分子的代谢，进而对WD载铜大鼠的神经损伤有一定的修复作用。
方法：将60只大鼠按随机数字表法分为4组，每组15只。即对照组，模型组，补肾活血化浊方组,和青霉胺组，随后根据文献方法复制WD载铜大鼠模型共12周。从第七周开始，每个干预组给予等效剂量的相应药物，对照组和模型组给予等量的生理盐水灌胃直至模型复制结束。我们使用1HNMR代谢组学技术结合多变量统计方法来描述Wilson病神经损伤的纹状体代谢谱的变化，并分析不同治疗方法对其生物标志物干预的影响。
结果：在WD载铜大鼠模型中神经细胞损伤明显，通过不同的干预方法对纹状体神经细胞均有不同程度的减轻。甘氨酸的含量，丝氨酸代谢，WD载铜大鼠模型缬氨酸代谢下降；青霉胺干预后天冬氨酸含量增加；糖酵解代谢，缬氨酸代谢，牛磺酸代谢,补肾活血化浊方组酪氨酸代谢增加。
结论：中西医不同干预方法对天冬氨酸,糖酵解,牛磺酸,酪氨酸,缬氨酸,WD载铜大鼠纹状体组织中的碳代谢，可以调节小分子的代谢，进而对WD载铜大鼠的神经损伤有一定的修复作用。
