Integrated Metabolomic and Lipidomic Analysis Reveals the Neuroprotective Mechanisms of Bushen Tiansui Formula in an Aβ1-42-Induced Rat Model of Alzheimer's Disease
Integrated Metabolomic and Lipidomic Analysis Reveals the Neuroprotective Mechanisms of Bushen Tiansui Formula in an Aβ1-42-Induced Rat Model of Alzheimer's Disease
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综合代谢组学和脂质组学分析揭示了补肾天髓方在 Aβ1-42 诱导的阿尔茨海默病大鼠模型中的神经保护机制
DOI：
10.1155/2020/5243453
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发表时间：
2020-06
影响因子：
--
通讯作者：
Weijun Peng
中科院分区：
文献类型：
--
作者：
Min Yi;Chunhu Zhang;Zheyu Zhang;Pengji Yi;Panpan Xu;Jianhua Huang;Weijun Peng
补肾天髓方（BSTSF）是一种中药方剂。临床上已广泛应用于治疗阿尔茨海默病（AD）；然而，其影响的机制仍然很大程度上未知。在本研究中，我们使用大鼠 AD 模型来研究 BSTSF 对认知能力的影响，并进一步进行基于 UPLC-MS/MS 的代谢组学和脂质组学分析，以确定 AD 大鼠大脑皮质中显着改变的代谢物，并确定 BSTSF 对这些动物大脑皮质代谢组学和脂质组学特征的影响。结果显示，AD大鼠大脑皮质中主要与鞘脂代谢、甘油磷脂代谢和亚油酸代谢相关的47种代谢物和30种脂质的水平发生显着变化。在改变的脂质中，神经酰胺、磷脂酰乙醇胺、溶血磷脂酰乙醇胺、磷脂酰胆碱、溶血磷脂酰胆碱、磷脂酰丝氨酸、鞘磷脂和磷脂酰甘油显示出强烈的变化。此外，34种差异内源代谢物和21种脂质，其中BSTSF治疗组的水平大部分得到改善，被确定为BSTSF治疗AD的潜在治疗靶点。我们的研究结果表明，AD大鼠大脑皮质脂质代谢高度失调，BSTSF可能通过恢复代谢平衡发挥其神经保护机制，包括鞘脂代谢、甘油磷脂代谢、丙氨酸、天冬氨酸和谷氨酸代谢，以及D-谷氨酰胺和D-谷氨酸代谢。我们的数据可能会让人们更深入地了解 AD 相关的代谢特征，并为 BSTSF 治疗作用的机制提供新的线索。
Bushen Tiansui Formula (BSTSF) is a traditional Chinese medicine prescription. It has been widely applied to treat Alzheimer’s disease (AD) in the clinic; however, the mechanisms underlying its effects remain largely unknown. In this study, we used a rat AD model to study the effects of BSTSF on cognitive performance, and UPLC-MS/MS-based metabolomic and lipidomic analysis was further performed to identify significantly altered metabolites in the cerebral cortices of AD rats and determine the effects of BSTSF on the metabolomic and lipidomic profiles in the cerebral cortices of these animals. The results revealed that the levels of 47 metabolites and 30 lipids primarily associated with sphingolipid metabolism, glycerophospholipid metabolism, and linoleic acid metabolism were significantly changed in the cerebral cortices of AD rats. Among the altered lipids, ceramides, phosphatidylethanolamines, lysophosphatidylethanolamines, phosphatidylcholines, lysophosphatidylcholines, phosphatidylserines, sphingomyelins, and phosphatidylglycerols showed robust changes. Moreover, 34 differential endogenous metabolites and 21 lipids, of which the levels were mostly improved in the BSTSF treatment group, were identified as potential therapeutic targets of BSTSF against AD. Our results suggest that lipid metabolism is highly dysregulated in the cerebral cortices of AD rats, and BSTSF may exert its neuroprotective mechanisms by restoring metabolic balance, including that of sphingolipid metabolism, glycerophospholipid metabolism, alanine, aspartate, and glutamate metabolism, and D-glutamine and D-glutamate metabolism. Our data may lead to a deeper understanding of the AD-associated metabolic profile and shed new light on the mechanism underlying the therapeutic effects of BSTSF.
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