基于多组学和网络分析探讨开心散改善D-Gal和a - β25 - 35诱导的AD大鼠认知缺陷的机制

IF 1.8 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS
Lifen Zhou, Min Zhang, Qin Zheng, Yonggui Song, Zhihong Yan, Huijuan Wang, Yongchang Xiong, Ying Chen, Zhinan Cai, Jinbin Yuan
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引用次数: 0

摘要

阿尔茨海默病(AD)是一种常见的神经退行性疾病,目前尚无有效药物治疗。开心散(KXS)疗效明确,在国内广泛应用于AD的防治。但其机制尚未完全了解。在我们建立的大鼠模型和前期药效学研究的基础上,结合多组学(代谢组学、蛋白质组学)和网络分析,探讨KXS抗ad作用的整体机制。采用western blot和ELISA方法对关键通路进行验证。Morris水迷宫和Nissl染色显示KXS可以改善AD大鼠的认知缺陷和海马的病理形态。共鉴定出9种代谢物,分别与嘧啶代谢、核黄素代谢、酪氨酸代谢、色氨酸代谢和甘油磷脂代谢有关。蛋白质组学结果表明,KXS对认知缺陷的改善与线粒体氧化磷酸化的调节密切相关。Western blotting结果显示,KXS显著抑制AD大鼠Mt-nd2和Ndufb6的表达。综合分析表明,KXS的抗ad靶点是相互关联的,KXS可能通过降低氧化应激、神经毒性和炎症来发挥其抗ad作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Exploring the Mechanism of Kai-Xin-San to Improve Cognitive Deficits in AD Rats Induced by D-Gal and Aβ25–35 Based on Multi-Omics and Network Analysis

Alzheimer's disease (AD) is a common neurodegenerative disease for which there are no effective drugs. Kai-Xin-San (KXS), with definite curative effects, is widely used for the prevention and treatment of AD in China. But its mechanism is not yet fully understood. Based on our established rat model and previous pharmacodynamics study, Multi-omics (metabolomics, proteomics) and network analysis were integrated to explore the holistic mechanism of anti-AD effects of KXS. The key pathways were validated with western blot and ELISA methods. Morris water maze and Nissl staining showed that KXS could ameliorate cognitive deficits and pathological morphology of the hippocampus in AD rats. A total of nine metabolites were identified, which were related to pyrimidine metabolism, riboflavin metabolism, tyrosine metabolism, tryptophan metabolism, and glycerophospholipid metabolism. Proteomics results indicated that the improvement of cognitive deficits by KXS was closely related to the regulation of oxidative phosphorylation in mitochondria. Western blotting results showed that KXS significantly inhibited the expression of Mt-nd2 and Ndufb6 in AD rats. Integrated analysis indicated that the anti-AD targets of KXS were interrelated and KXS could exert its anti-AD effect by reducing oxidative stress, neurotoxicity, and inflammation.

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来源期刊
Biomedical Chromatography
Biomedical Chromatography 生物-分析化学
CiteScore
3.60
自引率
5.60%
发文量
268
审稿时长
2.3 months
期刊介绍: Biomedical Chromatography is devoted to the publication of original papers on the applications of chromatography and allied techniques in the biological and medical sciences. Research papers and review articles cover the methods and techniques relevant to the separation, identification and determination of substances in biochemistry, biotechnology, molecular biology, cell biology, clinical chemistry, pharmacology and related disciplines. These include the analysis of body fluids, cells and tissues, purification of biologically important compounds, pharmaco-kinetics and sequencing methods using HPLC, GC, HPLC-MS, TLC, paper chromatography, affinity chromatography, gel filtration, electrophoresis and related techniques.
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