| 基于UHPLC-Q/TOF-MS代谢组学策略的葛根-知母药对防治阿尔茨海默病的药效与作用机制研究 |
| 投稿时间：2024-09-13 修订日期：2024-11-06 点此下载全文 |
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| 基金项目:国家自然科学基金项目(82173777) |
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| 中文摘要:目的 运用LC-MS血清代谢组学策略评价葛根-知母药对防治阿尔茨海默病(Alzheimer’s disease, AD)的药效并探讨其潜在作用机制。方法 采用氯化铝(AlCl3)和D-半乳糖(D-gal)联合给药20周建立AD大鼠模型,中药干预组分别予以葛根、知母和葛根-知母药对提取液灌胃8周,通过Morris水迷宫实验和超氧化物歧化酶(SOD)、一氧化氮(NO)以及丙二醛(MDA)等生化指标评价模型效果和药效；开展基于UHPLC-Q/TOF-MS法的代谢组学研究,并通过MetaboAnalyst在线网站分析相关代谢通路。结果 AD模型组大鼠学习和记忆能力较对照组显著下降,氧化应激和脂质过氧化物水平显著升高(P＜0.05),SOD含量显著降低(P＜0.01),葛根-知母药对干预能显著改善AD模型大鼠的学习记忆能力,逆转氧化应激和脂质过氧化水平,提高血清SOD含量,且效果优于单药。通过代谢组学鉴定出70种差异代谢物,主要涉及苯丙氨酸、酪氨酸和色氨酸生物合成、苯丙氨酸代谢、不饱和脂肪酸的生物合成等10条通路,葛根-知母药对干预可以回调其中47种代谢物,20种代谢物水平显著回调(P＜0.05),涉及苯丙氨酸、酪氨酸和色氨酸生物合成等6条通路。结论 葛根-知母药对能够显著改善AD大鼠模型的学习和记忆能力,其作用机制可能与改善氧化应激和脂质过氧化水平,增加血清SOD含量,调节苯丙氨酸、酪氨酸和色氨酸生物合成等通路相关。 |
| 中文关键词:阿尔茨海默病 代谢组学 葛根-知母 中药药对 作用机制 |
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| Study on the Pharmacological Effects and Mechanism of Gegen-Zhimu Herb Pair in Preventing and Treating Alzheimer |
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| Abstract:Objective The LC-MS serum metabolomics strategy was used to evaluate the efficacy of Puerariae lobatae radix (PLR) and Anemarrhenae Rhizoma (AR) in preventing and treating Alzheimer"s disease (AD) and explore its potential mechanism of action. Methods The AD rat model was established by administering aluminum chloride (AlCl3) and D-galactose (D-gal) for 20 weeks. The traditional Chinese medicine intervention group was given the PLR, AR, and PLR-AR extracts for 8 weeks by gavage. The model effect and efficacy were evaluated by Morris water maze test and biochemical indicators such as SOD, NO, and MDA; Metabolomics research based on the UHPLC-Q/TOF-MS method was conducted and relevant metabolic pathways were analyzed through the MetaboAnalyst online website. Results The learning and memory abilities of AD model rats were significantly decreased compared with the control group, and the levels of oxidative stress and lipid peroxides were significantly increased (P<0.05), while the SOD content was significantly decreased (P<0.01). The intervention of PLR-AR significantly improved the learning and memory abilities of AD model rats, reversed oxidative stress and lipid peroxidation levels, and increased serum SOD content, with better effects than single drugs. Through metabolomics, 70 differential metabolites were identified, mainly involving 10 pathways such as phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, and unsaturated fatty acid biosynthesis. The intervention of PLR-AR can adjust 47 metabolites, with 20 metabolites significantly adjusted (P<0.05). The significantly adjusted metabolites involve 6 pathways such as phenylalanine, tyrosine, and tryptophan biosynthesis. Conclusion The combination of PLR and AR can significantly improve the learning and memory abilities of AD rat models. The mechanism may be related to the improvement of oxidative stress and lipid peroxidation levels, the increase of serum SOD content, and the regulation of phenylalanine, tyrosine, and tryptophan biosynthesis pathways. |
| keywords:metabolomics Gegen-Zhimu herb pair mechanism Alzheimer's disease |
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