陆军军医大学学报2026，Vol.48Issue(5)：551-562,12.DOI:10.16016/j.2097-0927.202512065
淫羊藿苷通过调控骨钙素改善AD模型小鼠认知损害及降低相关亢进内分泌激素水平
Icariin ameliorates cognitive impairment and decreases hyperactive endocrine hormone levels in Alzheimer's disease mice by regulating osteocalcin secretion
摘要
Abstract
Objective To investigate whether icariin(ICA)ameliorates cognitive impairment and modulates relevant endocrine hormone alterations in Alzheimer's disease(AD)model mice by regulating osteocalcin(OCN)secretion.Methods An AD mouse model was established by intraventricular injection of okadaic acid(OA).Using a stratified design,4-week-old male SPF mice(weighing 18 to 22 g)were randomly divided into 8 groups(n=6):wild-type(WT)control group(intragastric administration of 60 mg/kg normal saline);WT-AD group(WT mice with left intracerebroventricular injection of 1 µL OA);WT+ICA group(60 mg/kg ICA daily);WT-AD+ICA group(WT-AD mice with daily 60 mg/kg ICA);OCN-/-control group(OCN-/-mice with 60 mg/kg normal saline);OCN-/--AD group(OCN-/-mice with left intracerebroventricular injection of 1 µL OA);OCN-/-+ICA group(OCN-/-mice with 60 mg/kg ICA daily);and OCN-/--AD+ICA group(OCN-/--AD mice with 60 mg/kg ICA daily).The Morris water maze test was conducted to assess learning and memory abilities,while open field test was performed to evaluate anxiety levels.Hippocampal histopathological changes were observed with HE staining and silver impregnation staining;Nissl bodies in hippocampal neurons were detected with Nissl staining.Immunohistochemistry assay was employed to determine the expression of amyloid β-protein(Aβ)and OCN,and Western blotting was used to measure the protein levels of Aβ and OCN.ELISA was applied to detect the expression levels of corticotropin-releasing hormone(CRH),glucose(GLU),glucocorticoid(GC),and cortisol(COR).Results Morris water maze test demonstrated that compared with the WT-AD group,the WT-AD+ICA group exhibited significantly shortened escape latency,prolonged time spent in the target quadrant,and increased platform crossing frequency(all P<0.05);similarly,the OCN-/--AD+ICA group showed improvements than the OCN-/--AD group(all P<0.05).Open field test results indicated that compared with the WT-AD group,the WT-AD+ICA group displayed significantly increased total exploration distance,distance in the center,and time in the center,enhanced activity willingness,and reduced time in peripheral zone and distance in peripheral zone(all P<0.05);similar improvements were observed in the OCN-/--AD+ICA group compared with the OCN-/--AD group(all P<0.05).Staining results revealed that ICA intervention attenuated hippocampal pathology,restored hippocampal morphological architecture,reduced neurofibrillary tangles(NFTs),and promoted gradual recovery of Nissl bodies;however,the OCN-/-mice failed to achieve complete normalization.Immunohistochemistry assay showed that compared with the WT-AD group,the WT-AD+ICA group exhibited decreased Aβ levels and increased OCN levels(all P<0.05);similar trends were observed in the OCN-/--AD+ICA group relative to the OCN-/--AD group(all P<0.05).Western blotting demonstrated that compared with the WT-AD group,the WT-AD+ICA group showed reduced Aβ expression and elevated OCN expression(both P<0.05);comparable changes were found in the OCN-/--AD+ICA group compared with the OCN-/--AD group(both P<0.05).ELISA indicated that compared with the WT-AD group,the WT-AD+ICA group exhibited significantly decreased levels of CRH,GLU,GC,and COR(all P<0.05);similar reductions were observed in the OCN-/--AD+ICA group compared with the OCN-/--AD group(all P<0.05).Conclusion ICA ameliorates cognitive impairment and reduces levels of related hyperactive endocrine hormones in AD model mice through regulating OCN secretion.关键词
阿尔茨海默病/淫羊藿苷/骨钙素/神经内分泌Key words
Alzheimer's disease/icariin/osteocalcin/neuroendocrine分类
医药卫生引用本文复制引用
崔曼,朱其凤,方兴,古联,闫雨,方俪霖,张明达,陈星宇..淫羊藿苷通过调控骨钙素改善AD模型小鼠认知损害及降低相关亢进内分泌激素水平[J].陆军军医大学学报,2026,48(5):551-562,12.基金项目
广西自然科学基金一般项目(2023GXNSFAA026458) （2023GXNSFAA026458）
国家自然科学基金地区科学基金项目(82260944) Supported by the General Project of Natural Science Foundation of Guangxi Zhuang Autonomous Region(2023GXNSFAA026458)and the Regional Science Fund Program of National Natural Science Foundation of China(82260944). （82260944）
