Untargeted metabolomics uncovering neuroprotective effect of Dl-3-n-butylphthalide on improving cognitive impairment induced by chronic cerebral hypoperfusion in rats
Untargeted metabolomics uncovering neuroprotective effect of Dl-3-n-butylphthalide on improving cognitive impairment induced by chronic cerebral hypoperfusion in rats
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DOI：
10.1016/j.intimp.2023.110271
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发表时间：
2023-05-10
影响因子：
5.6
通讯作者：
Zheng，Yangmin
中科院分区：
文献类型：
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作者：
Zhao，Fangfang;Zhong，Liyuan;Zheng，Yangmin
慢性脑灌注不足（CCH）可导致认知障碍。DL-3-正丁基苯酞（NBP）广泛用于神经系统疾病;但NBP在CCH中的作用尚不清楚。本研究旨在通过非靶向代谢组学研究NBP对CCH的作用机制。动物分为CCH组、Sham组和NBP组。采用大鼠双侧颈总动脉结扎模型模拟CCH。采用Morris水迷宫实验评价大鼠的认知功能。此外，我们使用LC-MS/MS检测三组之间代谢物的离子强度，用于脱靶代谢分析，并筛选差异代谢物。分析显示，NBP治疗后大鼠的认知功能有所改善。此外，代谢组学研究表明，假手术组和CCH组的血清代谢谱发生了显着改变，并确定了33种代谢产物作为与NBP的作用相关的潜在生物标志物。这些代谢物在24条代谢途径中富集，并通过免疫荧光进一步验证了差异代谢物富集途径。本研究为CCH的发病机制及NBP治疗CCH提供了理论依据，为NBP药物的广泛应用提供了支持。
Chronic cerebral hypoperfusion (CCH) can cause cognitive impairments. Dl-3-n-butylphthalide (NBP) is widely used in neurological disorders; but, the role of NBP in CCH remains unclear. This study aimed to investigate the potential mechanism of NBP on CCH through untargeted metabolomics. Animals were divided into CCH, Sham, and NBP groups. A rat model of bilateral carotid artery ligation was used to simulate CCH. Cognitive function of the rats was assessed using the Morris water maze test. Additionally, we used LC-MS/MS to detect ionic intensities of metabolites between the three groups for off-target metabolism analysis and to screen for differential metabolites. The analysis showed an improvement in cognitive function in rats after NBP treatment. Moreover, metabolomic studies showed that the serum metabolic profiles of the Sham and CCH groups were significantly altered, and 33 metabolites were identified as potential biomarkers associated with the effects of NBP. These metabolites were enriched in 24 metabolic pathways.And the pathway of differential metabolite enrichment was further verified by immunofluorescence. Thus, the study provides a theoretical basis for the pathogenesis of CCH and the treatment of CCH by NBP, and supports a wider application of NBP drugs.