机构地区：[1]Department of Geriatrics,Hunan Provincial People’s Hospital,The First Affiliated Hospital of Hunan Normal University,Changsha,Hunan 410005,China [2]Department of Integrated Traditional Chinese&Western Medicine,National Clinical Research Center for Metabolic Diseases,The Second Xiangya Hos-pital,Central South University,Changsha,Hunan 410011,China [3]Teaching and Research Section of Clinical Nursing,National Clinical Research Center for Geriatric Disorders,Xiangya Hospital,Central South Universi-ty,Changsha,Hunan 410008,China
出 处：《Digital Chinese Medicine》2024年第3期284-293,共10页数字中医药（英文）
基 金：Hunan Provincial Natural Science Foundation of China(2022JJ40220);Health Commission of Hunan Province(B202303106781);Hunan Administration of Traditional Chinese Medicine(2021192).
摘 要：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),Aβ_(25-35) group(treated with 20μmol/L Aβ_(25-35) for 24 h),icariin group(pre-treated with 20μmol/L icariin for 60 min,followed by 20μmol/L Aβ_(25-35) for an additional 24 h),and icariin+LY294002 group[treated with 20μmol/L icariin and 20μmol/L LY294002(an inhibitor of the phosphoinostitide 3-kinases(PI3K)signaling pathway)for 60 min,then exposed to 20μmol/L Aβ_(25-35) 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 uni目的探讨补肾填髓方及其活性成分淫羊藿苷对阿尔茨海默病(AD)的治疗作用及其机制。方法(1)动物实验。本研究使用无特定病原体(SPF)级别的雄性C57BL/6J野生型(WT)小鼠和APP/PS1双转基因小鼠进行实验,将小鼠分为WT组(WT小鼠,n=5,每日给予蒸馏水)、APP/PS1组(APP/PS1双转基因小鼠,n=5,每日给予蒸馏水)和BSTSD组[APP/PS1双转基因小鼠,n=5,以27 g/(kg·d)的剂量给予BSTSD悬浮液治疗90天]。采用Morris水迷宫(MWM)评估认知功能。实验后收集海马组织,通过苏木精-伊红(HE)染色和透射电子显微镜(TEM)分析锥体细胞和突触形态。(2)细胞实验。将HT-22细胞分为对照组(未处理)、Aβ_(25-35)组(用20μmol/L Aβ_(25-35)处理24小时)、淫羊藿苷组(先用20μmol/L淫羊藿苷预处理60分钟,然后用20μmol/L Aβ_(25-35)再处理24小时)以及淫羊藿苷+LY294002组[用20μmol/L淫羊藿苷和20μmol/L LY294002,一种磷脂酰肌醇-3-激酶(PI3K)信号通路抑制剂,处理60分钟,然后暴露于20μmol/L Aβ_(25-35)24小时],并测量细胞活力。使用Western blot检测突触相关蛋白[突触素(SYP)和突触后密度蛋白-95(PSD-95)]和PI3K信号通路相关蛋白[磷酸化(p)-PI3K/PI3K、p-蛋白激酶(Akt)/Akt和p-哺乳动物雷帕霉素靶蛋白(mTOR)/mTOR)]的表达水平。结果(1)动物实验。与APP/PS1组相比,BSTSD组显示出逃避潜伏期显著缩短(P<0.01),越过原始平台的频率显著增加(P<0.01)。形态学观察显示,BSTSD治疗后海马CA1区锥体细胞排列更规则,核染色均匀,空泡样变化减少。TEM显示,与APP/PS1组相比,BSTSD治疗组的突触活动区长度增加(P<0.01),突触间隙宽度减少(P<0.01)。(2)细胞实验。淫羊藿苷在不超过20μmol/L的浓度下对HT-22细胞无明显毒性(P>0.05),并且能够缓解Aβ_(25-35)诱导的细胞活力下降(P<0.01)。Western blot结果显示,与Aβ_(25-35)组相比,淫羊藿苷组的p-PI3K/PI3K、p-Akt/Akt和p-mTOR/mTOR的比值显著增加(P<0.01),而SYP和PSD-95的蛋白
关 键 词：Alzheimer’s disease(AD) Synapses Bushen Tiansui Decoction(补肾填髓方 BSTSD) ICARIIN Phosphoinostitide 3-kinases(PI3K)
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