数字中医药（英文）2024，Vol.7Issue(3)：284-293,10.DOI:10.1016/j.dcmed.2024.12.008
补肾填髓方通过PI3K信号通路调节阿尔茨海默病模型中的突触损伤
Modulation of synaptic damage by Bushen Tiansui Decoction via the PI3K signaling pathway in an Alzheimer's disease model
摘要
Abstract
Objective To explore the therapeutic effect and mechanism of Bushen Tiansui Decoction(补肾填髓方,BSTSD)and its active component icariin on Alzheimer's disease(AD). Methods(i)Animal experiments.This study conducted experiments using specific pathogen-free(SPF)grade male C57BL/6J wild-type(WT)mice and APP/PS1 double transgenic mice.The animals were divided into three groups:WT group(WT mice,n=5,receiving distilled wa-ter daily),APP/PS1 group(APP/PS1 double transgenic mice,n=5,receiving distilled water daily),and BSTSD group[APP/PS1 double transgenic mice,n=5,treated with BSTSD suspen-sion at a dosage of 27 g/(kg·d)for 90 d].Cognitive function was assessed using the Morris wa-ter maze(MWM).Post-experiment,hippocampal tissues were collected for analysis of pyra-midal cell and synaptic morphology through hematoxylin-eosin(HE)staining and transmis-sion electron microscopy(TEM).(ii)Cell experiments.The HT-22 cells were divided into con-trol group(untreated),Aβ25-35 group(treated with 20 μmol/L Aβ25-35 for 24 h),icariin group(pre-treated with 20 μmol/L icariin for 60 min,followed by 20 μmol/L Aβ25-35 for an additional 24 h),and icariin+LY294002 group[treated with 20 μmol/L icariin and 20 μmol/L LY294002(an inhibitor of the phosphoinostitide 3-kinases(PI3K)signaling pathway)for 60 min,then exposed to 20 μmol/L Aβ25-35 for 24 h],and cell viability was measured.Western blot was used to detect the expression levels of synapse-associated proteins[synaptophysin(SYP)and post-synaptic density-95(PSD-95)]and PI3K signaling pathway associated proteins[phosphorylat-ed(p)-PI3K/PI3K,p-protein kinase B(Akt)/Akt,and p-mechanistic target of rapamycin(mTOR)/mTOR]. Results(i)Animal experiments.Compared with APP/PS1 group,BSTSD group showed that escape latency was significantly shortened(P<0.01)and the frequency of crossing the origi-nal platform was significantly increased(P<0.01).Morphological observation showed that pyramidal cells in the hippocampal CA1 region were arranged more regularly,nuclear stain-ing was uniform,and vacuole-like changes were reduced after BSTSD treatment.TEM showed that the length of synaptic active zone in BSTSD treatment group was increased com-pared with APP/PS1 group(P<0.01),and the width of synaptic gap was decreased(P<0.01).(ii)Cell experiments.Icariin had no obvious toxicity to HT-22 cells when the concentration was not more than 20 μmol/L(P>0.05),and alleviated the cell viability decline induced by Aβ25-35(P<0.01).Western blot results showed that compared with Aβ25-35 group,the ratios of p-PI3K/PI3K,p-Akt/Akt and p-mTOR/mTOR in icariin group were significantly increased(P<0.01),while the protein expression levels of SYP and PSD-95 were increased(P<0.01).These effects were blocked by LY294002(P<0.01). Conclusion BSTSD and icariin enhance cognitive function and synaptic integrity in AD mod-els and provide potential therapeutic strategies through activation of the PI3K/Akt/mTOR pathway.关键词
阿尔茨海默病/突触/补肾填髓方/淫羊藿苷/磷脂酰肌醇3激酶(PI3K)Key words
Alzheimer's disease(AD)/Synapses/Bushen Tiansui Decoction(补肾填髓方,BSTSD)/Icariin/Phosphoinostitide 3-kinases(PI3K)引用本文复制引用
惠珊,郑庆,李宏丽,朱乐枚,吴蓓蓓,梁力晖,杨静静..补肾填髓方通过PI3K信号通路调节阿尔茨海默病模型中的突触损伤[J].数字中医药（英文）,2024,7(3):284-293,10.基金项目
Hunan Provincial Natural Science Foundation of China(2022JJ40220),Health Commission of Hunan Province(B202303106781),and Hunan Administration of Tradi-tional Chinese Medicine(2021192). （2022JJ40220）
