海南医科大学学报2025，Vol.31Issue(8)：589-598,10.DOI:10.13210/j.cnki.jhmu.20250326.004
基于代谢组学分析安神定志方抑制神经炎症治疗阿尔茨海默病的机制研究
Metabolic profiling analysis of the mechanism of Anshen Dingzhi Fang in inhibiting neuroinflammation for the treatment of Alzheimer's disease
摘要
Abstract
Objective:To observe the effects of Anshen Dingzhi Fang(ADF)on the serum metabolic profile of rats with Al-zheimer's disease(AD)and to further elucidate the molecular mechanisms by which this formula inhibits neuroinflammation and treats AD through cellular studies.Methods:A total of 30 Sprague-Dawley rats were randomly divided into a sham operation group,a model group,and an ADF group.The AD rat model was established by intracerebroventricular injection of Aβ1-42,and the rats were treated with corresponding medications for four weeks.Histopathological changes in the hippocampus were observed by H&E,Nissl,immunohistochemistry,and immunofluorescence staining to assess neuronal apoptosis and senile plaque forma-tion.Serum metabolomics was analyzed using untargeted metabolomics techniques,including principal component analysis,or-thogonal partial least squares-discriminant analysis,and differential metabolite screening to identify the effects of ADF on serum metabolites.Additionally,BV2 cells were divided into a control group,a lipopolysaccharide(LPS)group,an ADF group,and a dihydrokaempferol group.The neuroinflammatory cell model was induced by LPS in all groups except the control group.Subse-quently,the ADF group was treated with serum containing ADF,while the dihydrokaempferol group received dihydrokaempferol treatment.Inflammatory cytokines,brain-derived neurotrophic factor(BDNF),and vascular endothelial growth factor(VEGF)expression levels were measured usingELISA,and RT-qPCR.Subsequently,BV2 cells were co-cultured with Neuro-2a neuronal cells to evaluate the effects of ADF and dihydrokaempferol on Neuro-2a cell viability and apoptosis via CCK-8 and immunofluores-cence assays.Results:Animal experiments showed that compared to the model group,ADF significantly improved pathological morphology in the hippocampal CA1 region,restored the number of Nissl bodies in the hippocampal CA1 region,inhibited the for-mation of senile plaques,and reduced neuronal apoptosis,with statistically significant differences(P<0.01).Metabolomic results revealed 813 differential metabolites between the sham operation group and the model group,and 774 differential metabolites be-tween the ADF group and the model group.After intersection,378 key differential metabolites were identified.Cell experiments demonstrated that compared with the LPS group,both ADF and dihydrokaempferolsignificantly suppressed the levels of inflamma-tory cytokines TNF-α,IL-1β,and IL-6 and upregulated BDNF and VEGF mRNA expression in BV2 cells(P<0.01).Addition-ally,ADF and dihydrokaempferol significantly enhanced Neuro-2a cell viability and inhibited apoptosis(P<0.01).Conclusion:ADF enhances serum levels of dihydrokaempferol,thereby inhibiting neuroinflammation and improving neuronal apoptosis to treat AD.关键词
安神定志方/阿尔茨海默病/代谢组学/神经炎症/二氢山柰酚Key words
Anshen Dingzhi Fang/Alzheimer's disease/Metabolomics/Neuroinflammation/Dihydrokaempferol分类
医药卫生引用本文复制引用
王欣波,齐明明,邵音,赵宇,朴勇洙..基于代谢组学分析安神定志方抑制神经炎症治疗阿尔茨海默病的机制研究[J].海南医科大学学报,2025,31(8):589-598,10.基金项目
This study was supported by the Natural Science Foundation of Heilongjiang(H2018063)and Heilongjiang Province Traditional Chinese Medicine Research Project(ZHY19-003) 黑龙江省自然科学基金面上项目(H2018063) （H2018063）
黑龙江省中医药科研项目(ZHY19-003) （ZHY19-003）
