中国实验方剂学杂志2026，Vol.32Issue(19)：13-21,9.DOI:10.13422/j.cnki.syfjx.20260109
基于"肾脑相济"理论探讨归肾丸对亚急性衰老模型小鼠学习记忆的作用机制
Deciphering Mechanism of Guishen Wan on Learning and Memory in A Sub-acute Aging Mouse Model via Kidney-brain Axis
摘要
Abstract
Objective:To evaluate the Effect of Guishen Wan on learning and memory ability in D-galactose-induced aging model mice and to explore the application of the"Kidney-Brain Coordination"theory in traditional Chinese medicine(TCM).Methods:An subacute aging mouse model was established by subcutaneous injection of D-galactose(200 mg·kg-1·d-1)into the neck and back of KM mice.The mice were then administered GuiShen Wan at high,medium,and low doses(18,9,4.5 g·kg-1·d-1)or donepezil(2 mg·kg-1·d-1),a standard clinical therapeutic agent for Alzheimer's disease,served as the positive control in this study,for 4 consecutive weeks.Learning and memory abilities were evaluated using the Morris water maze.The degree of renal fibrosis was observed via Masson staining.Hippocampal neuron injury was assessed by hematoxylin-eosin(HE)staining.Damage to Nissl bodies in the hippocampus was examined using Nissl staining.The fluorescence expression intensity of Klotho in the hippocampus was detected by immunofluorescence.Western blot was used to detect the protein expression of Klotho in the kidneys,as well as proteins related to the hippocampal inflammatory pathway and inflammatory factor-related signaling pathways.Results:Results from the water maze test showed that compared with the blank group,the number of platform crossings and the time spent in the target quadrant were significantly decreased in the model group(P<0.01).Compared with the model group,all dose groups of Guishen Wan significantly increased the number of platform crossings and the time spent in the target quadrant in model mice(P<0.01).Masson staining results showed that compared with the blank group,the collagen volume fraction was significantly increased in the model group(P<0.01).Compared with the model group,all dose groups of Guishen Wan significantly reduced the collagen volume fraction in the model group(P<0.01).Kidney Western blot analysis showed that compared with the blank group,the Klotho protein was significantly decreased in the model group(P<0.01).Compared with the model group,Guishen Wan elevated the klotho protein(P<0.01).Neuronal cell count results showed that compared with the blank group,the number of neurons was significantly reduced in the model group(P<0.01).Compared with the model group,Guishen Wan exhibited a dose-dependent trend in repairing neuronal damage and increasing the number of neuronal cells(P<0.01).Immunofluorescence intensity results showed that compared with the blank group,the positive expression of Klotho was significantly decreased in the model group(P<0.01).Compared with the model group,all dose groups of Guishen Wan enhanced Klotho fluorescence expression(P<0.01).Hippocampal Western blot analysis showed that compared with the blank group,the ratios of interleukin(IL)-1β and IL-6 proteins were significantly increased in the model group(P<0.01).Compared with the model group,all dose groups of Guishen Wan significantly reduced the ratios of IL-1β and IL-6 proteins(P<0.01).Compared with the blank group,the ratio of phosphorylated-nuclear transcription factor-κB(p-NF-κB)protein was significantly increased(P<0.01),while the klotho protein was significantly decreased(P<0.01)in the model group.Compared with the model group,all Guishen Wan groups significantly reduced the p-NF-κB protein(P<0.05,P<0.01)and significantly increased the Klotho protein(P<0.01).Conclusion:Guishen Wan effectively ameliorates D-galactose-induced aging in model mice.Its mechanism of action may be related to upregulating Klotho concentration and inhibiting inflammatory factors associated with the NF-κB signaling pathway.关键词
归肾丸/抗衰老/克老素蛋白(Klotho)/炎症/学习记忆Key words
Guishen Wan/anti-aging/Klotho/inflammation/learning and memory分类
医药卫生引用本文复制引用
公佩帅,王平..基于"肾脑相济"理论探讨归肾丸对亚急性衰老模型小鼠学习记忆的作用机制[J].中国实验方剂学杂志,2026,32(19):13-21,9.基金项目
湖北省中央引领地方科技发展项目(2020ZYYD021) （2020ZYYD021）
中医脑健康理论传承创新及应用研究项目(湖北中医药大学2024年度科技创新项目) （湖北中医药大学2024年度科技创新项目）
中医药传承与创新"百千万"人才工程(岐黄工程)——国家中医药领军人才支持计划项目(国中医药人教发[2018]12号) （岐黄工程）
