蛋白质酪氨酸激酶2通过PI3K/AKT/Gsk3b信号调控Tau磷酸化

目的 探究蛋白质酪氨酸激酶2(protein tyrosine kinase,Pyk2)在学习记忆障碍小鼠模型中的表达及对神经元细胞Tau蛋白磷酸化的影响和分子机制.方法 免疫组化检测APPswe/PS1ΔE9(APP/PS1)双转基因AD和WT小鼠脑组织Pyk2蛋白表达;免疫印迹检测Pyk2、Tau5、Tau46、C...     

维生素E对D-半乳糖诱致衰老小鼠脑抗氧化能力、钙稳态和线粒体DNA（mtDNA）损伤的影响

目的：探讨维生素E（Vit-E）对D-半乳糖诱致衰老小鼠脑抗氧化能力、胞浆游离Ca²⁺（［Ca²⁺］i）稳态和线粒体DNA（mtDNA）损伤的影响。方法:小鼠连续皮下注射（sc）D-半乳糖（1 000 mg·k^-1·d^-1）8周制备衰老模型，并于第3周开始给予维生素E（100 mg· kg^-1；250 mg· kg^-1）处理；8周后采用水迷宫测定小鼠学习记忆能力，并取脑组织测定谷胱甘肽过氧化物酶(GSH-Px)和琥珀酸脱氢酶（SDH）活性，测定一氧化氮（NO）含量和一氧化氮合酶（NOS）活性。Fura-2/AM负载法和PCR方法分别测定海马神经细胞［Ca²⁺］i浓度和mtDNA缺失突变。结果:维生素E处理能明显改善D-半乳糖诱致衰老小鼠学习记忆障碍，抑制脑组织NOS活性，降低NO含量，提高GSH-Px和SDH活性，降低［Ca²⁺］i水平（P＜0.01， P＜0.05），并防止mtDNA缺失突变的发生。结论:维生素E具有提高衰老小鼠脑抗氧化能力和调节［Ca²⁺］i稳态的作用，并抑制氧化应激引起的mtDNA损伤，从而改善衰老动物学习记忆障碍。     

β淀粉样蛋白及代谢酶类在阿尔茨海默病和糖尿病模型小鼠脑内的表达

目的观察阿尔茨海默病(AD)和糖尿病模型小鼠脑内β淀粉样蛋白(Aβ)及代谢相关酶类的表达情况,以便从分子水平找到糖尿病并发AD的实验室依据。方法 5月龄双转基因痴呆症模型小鼠(APP/PS1双转基因小鼠)、ob/ob T2DM肥胖模型小鼠和野生型C57BL/6J小鼠为对照,分别用免疫组化染色、ELISA和Western blot检测脑内老年斑(SP)、Aβ含量及Aβ代谢酶类的表达情况。结果 APP/PS1小鼠大脑皮质及海马均可见一定数量的SP;ob/ob小鼠大脑皮质内偶可见SP,而对照组未见SP。与对照小鼠相比,APP/PS1与ob/ob小鼠脑内Aβ40、Aβ42的含量明显升高(P0.05);但APP/PS1小鼠脑内Aβ水平显著高于ob/ob小鼠(P0.05)。APP在APP/PS1小鼠脑内的表达显著高于其他两组小鼠;在ob/ob小鼠脑内的表达要强于对照小鼠(P0.05)。Aβ生成的关键酶BACE1在APP/PS1与ob/ob小鼠脑内的表达显著高于对照小鼠(P0.05),但其在APP/PS1小鼠脑内的表达要强于ob/ob小鼠(P0.05)。Aβ降解的关键酶IDE在APP/PS1与ob/ob小鼠脑内的表达显著低于对照小鼠(P0.05),且在ob/ob小鼠脑内表达最低。结论 Aβ生成与降解的异常以及其异常聚集沉积不仅发生在早期AD脑内,同时也发生在T2DM脑内,提示Aβ过表达可能是促进2型糖尿病并发AD的重要原因之一。     

盐酸多奈派齐对APP/PSl双转基因AD小鼠海马PI3K表达的影响美满霉素对帕金森病大鼠黑质多巴胺能神经元损伤的保护作用

目的本实验利用APP/PS1双转基因阿尔茨海默病(AIzheimer disease,AD)小鼠模型,观察盐酸多奈派齐对AD小鼠学习记忆能力及海马磷脂酰肌醇3激酶(phosphoinositide 3-kinases,PI3K)表达的影响。方法 APP/PS1双转基因模型小鼠20只,随机分为AD模型组(10)和盐酸多奈派齐组(10),再取同窝阴性小鼠10只,作为对照组。经跳台试验和水迷宫试验进行行为学测试,用免疫组化方法检测各组小鼠海马PI3K的表达变化。结果与对照组相比,AD模型组小鼠的学习和记忆成绩明显降低(<0.05);相比于AD模型组小鼠,盐酸多奈哌齐组小鼠的学习和记忆成绩明显提高(<0.05)。免疫组化检测结果证明,盐酸多奈哌齐组小鼠和对照组小鼠海马PI3K蛋白阳性表达明显增加,平均光密度值分别为(0.48±0.19)和(0.74±0.22),显著高于AD模型组(0.31±0.10,<0.05)。Western blot结果发现,盐酸多奈哌齐组小鼠和对照组小鼠海马PI3K蛋白的平均光密度值分别为(0.39±0.09)和(0.61±0.21),显著高于AD模型组(0.26±0.07,<0.05)。结论 AD小鼠海马区PI3K的表达上调可能是盐酸多奈哌齐改善AD小鼠学习和记忆功能的机制之一。     

APPswe/PS1dE9双转基因阿尔茨海默病模型小鼠的行为学及病理学特征研究

目的:探讨不同月龄APPswe/PS1dE 9双转基因小鼠行为学及病理学的变化特征,为合理运用该模型研究阿尔茨海默病提供可靠依据。方法:采用旷场实验、新物体辨别实验、Y迷宫以及Morris水迷宫等行为学实验方法观察不同月龄的APP/PS1转基因小鼠的运动、新物体辨别以及学习记忆能力的变化;通过免疫组织化学方法检测不同月龄转基因小鼠脑内Aβ含量及星形胶质细胞数量等病理特征的变化。结果:APPswe/PS1dE 9双转基因小鼠的运动能力随月龄增加逐渐下降,9月龄时对新物体的识别、工作记忆及空间学习记忆能力均出现明显损害。同时,该转基因小鼠的海马在6月龄时开始出现Aβ沉积和星形胶质细胞数量增加,9月龄时各种病理变化更为明显。结论:APPswe/PS1dE 9双转基因小鼠在6月龄时开始出现脑内病理改变,9月龄时各种认知行为发生明显异常。提示该转基因小鼠脑内病理改变可能早于行为异常,因此可根据实验目的选取相应月龄的动物。     

p21活化激酶在APP/PS1转基因AD小鼠模型海马内表达的年龄变化(英文)

阿尔茨海默病(Alzheimer's disease,AD)与突触障碍密切相关,p21活化激酶(p21-activated kinase,PAK)在突触功能调节中起重要作用。然而,PAK与AD病理学变化之间的关系,尚不清楚。本实验用分子生物学及组织化学等方法检测了不同周龄APP/PS1转基因AD小鼠模型海马中PAK3(PAK的代表性亚型)、pPAK(磷酸化的PAK)和Aβ42(含42个氨基酸片断的Aβ多肽)的表达水平以及神经元的形态学变化。Western Blot结果显示,海马中PAK3的表达,在不同年龄的APP/PS1转基因AD模型小鼠和非转基因小鼠中,均没有显著性差别;而pPAK表达则出现显著性降低(32周),并且随年龄增长进一步下降。Aβ42的水平在转基因AD小鼠模型海马中增加较早(22周),并随年龄的增长而显著增加。Nissl染色显示,转基因AD小鼠模型海马神经元无明显数量变化;而Golgi银染法显示,转基因AD小鼠模型海马神经元的树突显著变形、紊乱。这些结果说明,在APP/PS1转基因AD小鼠模型PAK表达正常,但PAK的磷酸化过程出现了异常,导致其活性不足。Aβ42的毒性作用可能是导致pPAK活性下降的原因,而pPAK的下降又可能是影响海马神经元树突发育、造成其变形、紊乱的直接原因。     

FSD-C10调节阿尔茨海默病双转基因小鼠炎性微环境

目的:探讨新型Rho激酶抑制剂FSD-C10对阿尔茨海默病(Alzheimer disease,AD)模型小鼠脑内炎性微环境的调节作用。方法:采用双转染人β-淀粉样蛋白前体(β-amyloid protein precursor,APP)695swe基因和人早老素1(presenilin-1,PS1)ΔE9突变基因的8月龄小鼠作为AD动物模型,随机分为模型组和FSD-C10治疗组,分别经腹腔注射生理盐水和FSD-C10(25 mg·kg~(-1)·d~(-1))持续治疗2个月,同月龄野生型小鼠作为正常对照组。应用Morris水迷宫(Morris water maze,MWM)实验检测小鼠学习和记忆能力。采用免疫组化和Western blot技术检测小鼠脑组织β-淀粉样蛋白(Aβ)、磷酸化Tau蛋白(p-Tau)、β位点APP剪切酶(BACE)、Toll样受体4(TLR-4)、磷酸化核因子κB(p-NF-κB)、诱导型一氧化氮合酶(i NOS)和精氨酸酶1(Arg-1)的表达。结果:与模型组相比,FSD-C10干预能显著改善APP/PS1双转基因小鼠学习和记忆能力,减少海马区Aβ1-42、p-Tau和BACE的表达,抑制脑内炎症信号通路TLRs/NF-κB轴TLR-4的表达和p-NF-κB的激活,减少i NOS的表达,增加Arg-1的表达。结论:FSD-C10干预能明显改善APP/PS1双转基因小鼠的学习和记忆能力,其机制可能是通过抑制TLRs/NF-κB信号通路激活,减少炎症因子的分泌及促进M1型炎性小胶质细胞向M2型抗炎小胶质细胞转化,从而改善APP/PS1双转基因小鼠脑组织炎症微环境。     

胰岛淀粉样多肽对阿尔茨海默病小鼠脑组织中LncRNA和mRNA表达谱的影响

目的:探讨胰岛淀粉样多肽（IAPP）对阿尔茨海默病（AD）小鼠脑组织中长链非编码RNA（LncRNA）和信使RNA（mRNA）表达谱的影响。方法:选取7月龄雄性APP/PS1转基因AD模型小鼠10只,体质量20～30 g。将AD模型小鼠按数字表法随机分为IAPP干预组和对照组,每组5只。IAPP干预组小鼠腹腔内注射0....     

阿尔茨海默病合并2型糖尿病模型小鼠海马血管损伤与认知改变

目的 探讨2型糖尿病（T2DM）对阿尔茨海默病（AD）脑血管发育的影响,及其对AD病理发生的影响机制。 方法 40只6月龄APP/PS1转基因小鼠及同窝野生型小鼠采用高糖高脂饲料喂养6个月后,即各组小鼠12月龄时,连续4 d腹腔注射 1% 链脲佐菌素溶液,建立AD合并T2DM模型小鼠及单纯T2DM模型小鼠。设立4个组别：正常对照组、AD组、T2DM组、AD合并T2DM组,每组小鼠各10只。通过小鼠跳台实验检测小鼠学习记忆能力,墨汁灌注观察小鼠海马区血管形态,油红O染色、免疫荧光实验检测小鼠海马区各病理指标变化。 结果 与正常对照组相比,AD合并T2DM模型小鼠学习与记忆能力明显下降(P<0.05),海马区血管变细、密度明显减低(P<0.05),脂质沉积增多并出现小血管渗漏,且其海马区β-淀粉样前体蛋白裂解酶1（BACE-1）、核因子（NF)-κB与基质金属蛋白酶（MMP)-9表达增多(P<0.05)。 结论 T2DM对小鼠学习记忆功能起负作用,通过促进AD病理变化加速AD模型小鼠脑血管病变,MMP-9的异常表达也可能是引起AD血管病变的原因之一。     

雷公藤甲素抑制APP/PS1双转基因AD模型小鼠海马内Aβ沉积和老年斑形成

目的 研究雷公藤甲素(T10)对APP/PS1双转基因AD模型小鼠(APP/PS1dtg)β-淀粉样蛋白(Aβ)沉积与老年斑(SP)形成的影响。 方法 取18只45月龄健康雄性APP/PS1dtg, 随机分为3组,分别以T10灌胃：5μg/(kg&#8226;d) (T10 H组)、1μg/(kg&#8226;d) (T10 L组)和等容量的溶媒灌胃（PLC组）,共计45d。45d后取材,左侧半大脑切片,6E10免疫组织化学方法染色和刚果红染色结合无偏性体视学定量分析,研究T10对海马Aβ沉积和SP形成的影响;分离右侧半海马,免疫印迹法分析海马Aβ蛋白水平的变化。 结果 与PLC组比较, T10 H组海马6E10阳性的Aβ沉积总面积减少了35％(P<0.001),SP总面积减少了32％(P<0.001); T10 L组海马Aβ斑总面积减少了18％(P<0.05), SP总面积减了21％(P<0.05); T10呈剂量依赖性抑制Aβ在APP/PS1dtg 海马的沉积和SP的形成,减少海马内Aβ蛋白水平; 免疫印迹分析也显示,T10 H组海马Aβ蛋白水平最低,PLC组Aβ蛋白水平最高,T10 L组Aβ蛋白水平介于两者之间。     

Voluntary Running Attenuates Memory Loss,Decreases Neuropathological Changes and Induces Neurogenesis in a Mouse Model of Alzheimer's Disease

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by loss of memory and cognitive abilities, and the appearance of amyloid plaques composed of the amyloid‐β peptide (Aβ) and neurofibrillary tangles formed of tau protein. It has been suggested that exercise might ameliorate the disease; here, we evaluated the effect of voluntary running on several aspects of AD including amyloid deposition, tau phosphorylation, inflammatory reaction, neurogenesis and spatial memory in the double transgenic APPswe/PS1ΔE9 mouse model of AD. We report that voluntary wheel running for 10 weeks decreased Aβ burden, Thioflavin‐S‐positive plaques and Aβ oligomers in the hippocampus. In addition, runner APPswe/PS1ΔE9 mice showed fewer phosphorylated tau protein and decreased astrogliosis evidenced by lower staining of GFAP. Further, runner APPswe/PS1ΔE9 mice showed increased number of neurons in the hippocampus and exhibited increased cell proliferation and generation of cells positive for the immature neuronal protein doublecortin, indicating that running increased neurogenesis. Finally, runner APPswe/PS1ΔE9 mice showed improved spatial memory performance in the Morris water maze. Altogether, our findings indicate that in APPswe/PS1ΔE9 mice, voluntary running reduced all the neuropathological hallmarks of AD studied, reduced neuronal loss, increased hippocampal neurogenesis and reduced spatial memory loss. These findings support that voluntary exercise might have therapeutic value on AD.     

Increased regional cerebral glucose uptake in an APP/PS1 model of Alzheimer's disease

Alzheimer's disease (AD), the most common age-related neurodegenerative disorder, is characterized by the invariant cerebral accumulation of β-amyloid peptide. This event occurs early in the disease process. In humans, [18F]-fluoro-2-deoxy-D-glucose ([18F]-FDG) positron emission tomography (PET) is largely used to follow-up in vivo cerebral glucose utilization (CGU) and brain metabolism modifications associated with the Alzheimer's disease pathology. Here, [18F]-FDG positron emission tomography was used to study age-related changes of cerebral glucose utilization under resting conditions in 3-, 6-, and 12-month-old APP(SweLon)/PS1(M146L), a mouse model of amyloidosis. We showed an age-dependent increase of glucose uptake in several brain regions of APP/PS1 mice but not in control animals and a higher [18F]-FDG uptake in the cortex and the hippocampus of 12-month-old APP/PS1 mice as compared with age-matched control mice. We then developed a method of 3-D microscopic autoradiography to evaluate glucose uptake at the level of amyloid plaques and showed an increased glucose uptake close to the plaques rather than in amyloid-free cerebral tissues. These data suggest a macroscopic and microscopic reorganization of glucose uptake in relation to cerebral amyloidosis.     

Curcumin Ameliorates Memory Deficits by Enhancing Lactate Content and MCT2 Expression in APP/PS1 Transgenic Mouse Model of Alzheimer's Disease

Curcumin is a natural product with several anti-Alzheimer's disease (AD) neuroprotective properties. This study aimed to investigate the effects of curcumin on memory deficits, lactate content, and monocarboxylate transporter 2 (MCT2) in APP/PS1 mouse model of AD. APP/PS1 transgenic mice and wild-type (WT) C57BL/6J mice were used in the present study. Spatial learning and memory of the mice was detected using Morris water-maze test. Cerebral cortex and hippocampus lactate contents were detected using lactate assay. MCT2 expression in the cerebral cortex and hippocampus was examined by immunohistochemistry and Western blotting. Results showed that spatial learning and memory deficits were improved in curcumin-treated APP/PS1 mouse group compared with those in APP/PS1 mice group. Brain lactate content and MCT2 protein level were increased in curcumin-treated APP/PS1 mice than in APP/PS1 mice. In summary, our findings indicate that curcumin could ameliorate memory impairments in APP/PS1 mouse model of AD. This phenomenon may be at least partially due to its improving effect on the lactate content and MCT2 protein expression in the brain. Anat Rec, 302:332–338, 2019. © 2018 Wiley Periodicals, Inc.     

Genotype-related changes of ganglioside composition in brain regions of transgenic mouse models of Alzheimer's disease

In this study, brain gangliosides of different transgenic mouse models of Alzheimer's disease (AD) were analyzed and compared with age-matched wild-type mice. Gangliosides were analyzed in cerebral cortex, a region with extensive Aβ plaques, and cerebellum, a non-vulnerable region with no Aβ containing plaques. There was a marked increase in simple gangliosides GM2 and GM3 only within the cortex of all mice expressing APP^SL. Additionally, loss of complex “a” gangliosides (GT1a, GD1a and GM1) was recorded in APP/PS1Ki model, whereas in APP^SL and APP/PS1 mice, the complex “b” gangliosides (GQ1b, GT1b and GD1b) moderately decreased. Surprisingly, expression of either mutant PS1^M146L or PS1 mutant FAD (Ki model) alone tended to lower the levels of both GM2 and GM3 within the cortex. Conversely, only slight changes of the ganglioside pattern were found in the cerebellum. Because ganglioside alterations occurring in APP transgenic mice were similar to those observed in human AD brain, these transgenic models would represent valuable tools to further investigate the role of altered ganglioside metabolism in the pathogenesis of AD.     

Beneficial effects of quetiapine in a transgenic mouse model of Alzheimer's disease

Previous studies have suggested that quetiapine, an atypical antipsychotic drug, may have beneficial effects on cognitive impairment, and be a neuroprotectant in treating neurodegenerative diseases. In the present study, we investigated the effects of quetiapine on memory impairment and pathological changes in an amyloid precursor protein (APP)/presenilin-1 (PS-1) double transgenic mouse model of Alzheimer's disease (AD). Non-transgenic and transgenic mice were treated with quetiapine (0, 2.5, or 5mg/(kg day)) for 1, 4, and 7 months in drinking water from the age of 2 months. After 4 and 7 months of continuous quetiapine administration, memory impairment was prevented, and the number of beta-amyloid (Abeta) plaques decreased in the cortex and hippocampus of the transgenic mice. Quetiapine also decreased brain Abeta peptides, beta-secretase activity and expression, and the level of C99 (an APP C-terminal fragment following cleavage by beta-secretase) in the transgenic mice. Furthermore, quetiapine attenuated anxiety-like behavior, up-regulated cerebral Bcl-2 protein, and decreased cerebral nitrotyrosine in the transgenic mice. These findings suggest that quetiapine can alleviate cognitive impairment and pathological changes in an APP/PS1 double transgenic mouse model of AD, and further indicate that quetiapine may have preventive effects in the treatment of AD.     

淀粉样蛋白前体/早老素1转基因小鼠大脑皮质内kinesin1介导的神经元轴浆运输障碍

目的 探讨轴突运输蛋白,kinesin1和神经丝蛋白（SIM-312）在阿尔茨海默病(AD)发生、发展中的作用。 方法 出生后30～360 d淀粉样蛋白前体（APP）/早老素1（PS1）转基因小鼠（n＝40）和野生型小鼠（n＝40）用于此研究,利用免疫荧光染色和Western blotting技术检测上述两种小鼠大脑皮层内老年斑的沉积及星形胶质细胞的分布以及在大脑皮质发育过程中kinesin1和SIM-312阳性细胞个数及蛋白的表达变化。 结果 APP/PS1转基因小鼠与正常对照组相比,β-淀粉样蛋白（Aβ）斑块增多,星形胶质细胞数目增多,神经元减少;而kinesin1阳性细胞的数量在APP/PS1转基因小鼠生长发育过程中减少,且在出生9月（P9M）之后与野生型小鼠之间差异存在着显著性 (P<0.05);SIM-312标记的神经丝蛋白随着年龄的增长自P6M之后开始出现缠结现象。 结论 Kinesin1和SIM-312的异常改变导致神经元中轴浆运输障碍以及AD的病理变化。     

DMT1在APP/PS1转基因小鼠大脑皮层老年斑内的定位研究

目的研究二价金属离子转运体1(divalent metal transporter 1,DMT1)在APP/PS1转基因小鼠大脑皮层内的定位分布,探讨DMT1异常表达影响脑铁代谢平衡从而参与AD发病的可能机制。方法应用免疫组织化学方法观察DMT1在9月龄APPsw/PS1小鼠大脑皮层的阳性分布;应用免疫荧光双标技术和共聚焦激光扫描显微镜观察DMT1蛋白和β淀粉样蛋白(β-amyloid peptide,Aβ)在APP/PS1转基因小鼠大脑皮层老年斑内的一致性分布和位置关系。结果APP/PS1转基因小鼠大脑皮层老年斑内均有DMT1阳性表达;DMT1和Aβ免疫双标发现DMT1免疫阳性产物与Aβ共存于老年斑,二者分布具有一致性。结论DMT1在APP/PS1转基因小鼠大脑皮层老年斑内大量表达,其分布与Aβ具有一致性,提示DMT1可能参与AD脑内Aβ沉积和老年斑形成。     

芍药苷对APP/PS1小鼠的神经细胞保护作用及机制研究

目的:探讨芍药苷(paeoniflorin,PF)通过抑制细胞凋亡通路而产生神经细胞保护作用的机制。方法:分别选用15只5月龄雄性APP/PS1非显性小鼠作为正常对照组,15只5月龄雄性APP/PS1双转基因小鼠为模型组和15只5月龄雄性APP/PS1双转基因小鼠为给药组(5 mg/kg的PF腹腔注射)。采用水迷宫实验检测各组小鼠的学习和记忆能力。采用TUNEL荧光染色法检测脑内神经细胞凋亡情况。采用Western Blot检测脑内皮层及海马区PI3K、Akt、p-PI3K、p-Akt、caspase-3、caspase-9、Bcl-2和Bax的蛋白表达水平,并用免疫组化分析caspase-3和caspase-9的蛋白表达水平及分布情况。结果:(1)与正常对照组相比,APP/PS1模型组小鼠的学习和记忆能力明显下降;与APP/PS1模型组相比,PF明显改善小鼠的学习和记忆能力。(2)与正常对照组相比,APP/PS1模型组小鼠脑内神经细胞凋亡明显增多,分布区域较广,而PF给药组小鼠凋亡细胞明显减少。(3)与APP/PS1模型组相比,PF给药组能显著下调促凋亡因子caspase-3、caspase-9和Bax的表达水平(P0.05),同时上调抑凋亡因子pPI3K、p-Akt和Bcl-2的表达水平(P0.05)。结论:PF可能通过激活PI3K/Akt通路而上调Bcl-2,下调caspase-9、caspase-3和Bax的蛋白表达水平,从而抑制神经细胞凋亡和保护神经细胞,以治疗神经退行性疾病。     

淫黄葛复合剂对阿尔茨海默病小鼠行为学和海马解聚素金属蛋白酶10表达的影响

目的 探讨淫羊藿、黄芪、葛根有效组分复方对阿尔茨海默病（AD）模型小鼠行为学和海马CA3区解聚素金属蛋白酶10（ADAM10）表达的影响。方法 10月的雄性APPswe/PS1dE9双转基因模型小鼠30只随机分为复方组、模型组和去铁斯诺(DFX)组,10月龄的雄性C57BL/6 J小鼠10只作为正常对照组。用药结束后,采用Morris水迷宫检测各组小鼠学习记忆能力,并于水迷宫后取出小鼠的脑组织,应用免疫荧光、Real-time PCR和Western blotting方法检测各组小鼠海马CA3区ADAM10的表达。结果 水迷宫实验结果显示,与正常对照组小鼠相比,模型组小鼠的逃避潜伏期、游泳距离和游泳时间均明显延长(P＜0.05),穿越平台区域次数和平台区域停留时间明显减少(P＜0.05),首次穿越平台的逃避潜伏期明显延长(P＜0.05);与模型组小鼠相比,复方组和DFX组逃避潜伏期、游泳距离和游泳时间明显缩短(P＜0.05),穿越平台区域次数和平台区域停留时间明显增多(P＜0.05),首次穿越平台的逃避潜伏期明显缩短;复方组和DFX组相比,逃避潜伏期、游泳距离和游泳时间及跨台次数差异无显著性 (P＞0.05),穿越平台区域次数、平台区域停留时间和首次穿越平台的逃避潜伏期差异无显著性 (P＞0.05)。与正常对照组小鼠相比,模型组小鼠海马CA3区ADAM10的表达增高(P＜0.05);与模型组相比,复方组和DFX组小鼠海马CA3区DAM10的表达降低(P＜0.05);复方组和DFX组相比,ADAM10表达水平差异无显著性 (P＞0.05)。结论 应用淫羊藿、黄芪、葛根有效组分复方可以改善APPswe/PS1dE9双转基因AD模型小鼠的学习记忆能力,其机制可能与下调ADAM10的表达减少神经元的损伤和死亡有关。