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Recent innovations in laser additive manufacturing of titanium alloys

International Journal of Extreme Manufacturing 2024年第3期6卷 2-37页

作者： Jinlong Su Fulin Jiang Jie Teng Lequn Chen Ming yan Guillermo Requena Lai-Chang Zhang y morris wang Ilya V Okulov Hongmei Zhu Chaolin Tan College of Materials Science and Engineering Hunan UniversityChangsha 410082People’s Republic of China Singapore Institute of Manufacturing Technology(SIM Tech) Agency for ScienceTechnology and Research(A∗STAR)5 Cleantech LoopSingapore 636732Singapore Department of Materials Science and Engineering Southern University of Science and TechnologyShenzhen 518055People’s Republic of China Institute of Materials Research German Aerospace Center(DLR)Linder Höhe51147 CologneGermany Centre for Advanced Materials and Manufacturing Edith Cowan University270 Joondalup DriveJoondalupPerthWestern Australia 6027Australia Department of Materials Science and Engineering University of CaliforniaLos AngelesCA 900095United States of America Leibniz Institute for Materials Engineering-IWT Badgasteiner Str.328359 BremenGermany Faculty of Production Engineering University of BremenBadgasteiner Str.128359 BremenGermany Key Laboratory of Hunan Province of Equipment Safety Service Technology under Extreme Environment University of South ChinaHengyangPeople’s Republic of China RWTH Aachen University Metallic Structures and Materials Systems for Aerospace EngineeringD-52062 AachenGermany

Titanium(Ti)alloys are widely used in high-tech fields like aerospace and biomedical *** additive manufacturing(LAM),as an innovative technology,is the key driver for the development of Ti *** the significant advancements in LAM of Ti alloys,there remain challenges that need further research and development *** recap the potential of LAM high-performance Ti alloy,this article systematically reviews LAM Ti alloys with up-to-date information on process,materials,and *** feasible solutions to advance LAM Ti alloys are reviewed,including intelligent process parameters optimization,LAM process innovation with auxiliary fields and novel Ti alloys customization for *** auxiliary energy fields(***,acoustic,mechanical deformation and magnetic fields)can affect the melt pool dynamics and solidification behaviour during LAM of Ti alloys,altering microstructures and mechanical *** kinds of novel Ti alloys customized for LAM,like peritecticα-Ti,eutectoid(α+β)-Ti,hybrid(α+β)-Ti,isomorphousβ-Ti and eutecticβ-Ti alloys are reviewed in ***,machine learning in accelerating the LAM process optimization and new materials development is also *** review summarizes the material properties and performance envelops and benchmarks the research achievements in LAM of Ti *** addition,the perspectives and further trends in LAM of Ti alloys are also highlighted.

关键词： additive manufacturing titanium alloys auxiliary field machine learning aerospace materials lightweight materials novel alloys

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SIL1 improves cognitive impairment in APP23/PS45 mice by regulating amyloid precursor protein processing and Aβ generation

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Zoological Research 2024年第4期45卷 845-856页

作者： Qunxian wang yanshuang Jiang Zijun Meng Xiangjun Dong Dongjie Hu Liangye Ji Weihui Zhou Weihong Song Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400000China Second Affiliated Hospital and yuying Children’s Hospital Institute of AgingKey Laboratory of Alzheimer’s Disease of Zhejiang ProvinceWenzhou Medical UniversityWenzhouZhejiang 325000China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)WenzhouZhejiang 325001China

SIL1,an endoplasmic reticulum(ER)-resident protein,is reported to play a protective role in Alzheimer’s disease(AD).However,the effect of SIL1 on amyloid precursor protein(APP)processing remains *** this study,the role of SIL1 in APP processing was explored both in vitro and in *** the in vitro experiment,SIL1 was either overexpressed or knocked down in cells stably expressing the human Swedish mutant *** the in vivo experiment,AAV-SIL1-EGFP or AAV-EGFP was microinjected into APP23/PS45 mice and their wild-type *** blotting(WB),immunohistochemistry,RNA sequencing(RNA-seq),and behavioral experiments were performed to evaluate the relevant *** indicated that SIL1 expression decreased in APP23/PS45 *** of SIL1 significantly decreased the protein levels of APP,presenilin-1(PS1),and C-terminal fragments(CTFs)of APP in vivo and in ***,knockdown of SIL1 increased the protein levels of APP,β-site APP cleavage enzyme 1(BACE1),PS1,and CTFs,as well as APP mRNA expression in 2EB2 ***,SIL1 overexpression reduced the number of senile plaques in APP23/PS45 ***,y-maze and morris Water maze tests demonstrated that SIL1 overexpression improved cognitive impairment in APP23/PS45 *** findings indicate that SIL1 improves cognitive impairment in APP23/PS45 mice by inhibiting APP amyloidogenic processing and suggest that SIL1 is a potential therapeutic target for AD by modulating APP processing.

关键词： Alzheimer’s disease SIL1 APP processing Cognitive impairment

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基于SIRT1/STAT3通路探讨盐酸戊乙奎醚对小鼠学习记忆能力的影响

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中国临床药理学杂志 2024年第10期40卷 1473-1477页

作者：汪静张庆国南方医科大学珠江医院麻醉科广东广州510280

目的探讨高剂量盐酸戊乙奎醚(PHC)对小鼠学习记忆能力的影响及其作用机制。方法将60只C57BL/6J小鼠随机分为对照组(腹腔注射等量的0.9%NaCl)、低剂量实验组(腹腔注射0.12 mg·kg^(-1)PHC)、高剂量实验组(腹腔注射5.00 mg·kg^(-1)PHC)、... 详细信息

目的探讨高剂量盐酸戊乙奎醚(PHC)对小鼠学习记忆能力的影响及其作用机制。方法将60只C57BL/6J小鼠随机分为对照组(腹腔注射等量的0.9%NaCl)、低剂量实验组(腹腔注射0.12 mg·kg^(-1)PHC)、高剂量实验组(腹腔注射5.00 mg·kg^(-1)PHC)、SRT1720组[腹腔注射5.00 mg·kg^(-1)PHC和5 mg·kg^(-1)沉默信息调节因子1(SIRT1)激活药SRT1720],每组15只。给药6 h后,用morris水迷宫实验和y迷宫实验检测小鼠学习记忆能力,用蛋白质印迹法检测小鼠海马组织中SIRT1和信号转导及转录激活因子3(STAT3)蛋白的表达水平,用试剂盒检测小鼠海马组织胆碱乙酰转移酶(ChAT)水平,用免疫荧光检测海马组织胶质纤维酸性蛋白(GFAP)阳性表达情况。结果对照组、低剂量实验组、高剂量实验组和SRT1720组小鼠给药6 h后穿越平台次数分别为(6.07±0.44)、(6.00±0.37)、(3.00±0.97)和(4.47±1.31)次,逃避潜伏期分别为(14.02±1.79)、(14.16±1.67)、(51.55±4.07)和(32.84±2.40)s,y迷宫交替率分别为(60.90±5.18)%、(59.38±5.99)%、(39.80±4.45)%和(46.65±5.02)%,SIRT1蛋白相对表达水平分别为1.05±0.09、1.08±0.12、0.52±0.07和0.77±0.11,STAT3蛋白相对表达水平分别为0.37±0.03、0.38±0.06、0.68±0.06和0.53±0.08,ChAT水平分别为(306.08±20.11)、(296.33±36.11)、(209.99±18.91)和(250.42±25.22)pg·mL-1,GFAP平均光密度值分别为0.05±0.00、0.05±0.00、0.08±0.01和0.06±0.01。高剂量实验组的上述指标与对照组比较,高剂量实验组的上述指标与低剂量实验组比较,SRT1720组的上述指标与高剂量实验组比较,在统计学上差异均有统计学意义(均P<0.05)。结论高剂量的PHC可能通过抑制SIRT1/STAT3通路导致小鼠学习记忆能力下降。

关键词：盐酸戊乙奎醚沉默信息调节因子1/信号转导及转录激活因子3信号学习记忆能力

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Incidence and risk of herpes zoster in patients with ulcerative colitis and Crohn’s disease in the USA

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Gastroenterology Report 2023年第1期11卷 271-281页

作者： David Singer Philippe Thompson-Leduc Deepshekhar Gupta Wendy y.Cheng Sara Poston Siyu Ma John E.Pawlowski Mei Sheng Duh Eric D.morris Francesca Devine Francis A.Farraye US Health Outcomes and Epidemiology—Vaccines GSKPhiladelphiaPAUSA Health Economics and Outcomes Research Analysis GroupInc.MontrealQuebecCanada Health Economics and Outcomes Research Analysis GroupInc.Menlo ParkCAUSA Health Economics and Outcomes Research Analysis GroupInc.BostonMAUSA Tufts Medical Center BostonMAUSA Medical Affairs GSKPhiladelphiaPAUSA Health Economics and Outcomes Research Analysis GroupInc.New YorkNYUSA Division of Gastroenterology and Hepatology Mayo ClinicJacksonvilleFLUSA

Background:Patients with inflammatory bowel disease(IBD)are at increased risk of herpes zoster(HZ).We evaluated the incidence of HZ in ulcerative colitis(UC)and Crohn’s disease(CD)patients and compared this with HZ incidence in a non-IBD ***:We conducted a retrospective cohort study(GSK study identifier:VEO-000043)of adults aged18 years with UC and CD and without IBD who were identified from claims recorded in a US healthcare database between October 2015 and February *** HZ incidence rates/1,000 person-years(Py)were calculated,and comparisons of HZ incidence rates between UC or CD and non-IBD cohorts were made using adjusted generalized linear ***:The study population comprised a total of 29,928 UC,25,959 CD,and 11,839,329 non-IBD *** overall HZ incidence rates were 13.64/1,000 Py(UC),15.94/1,000 Py(CD),and 7.95/1,000 Py(non-IBD).UC and CD patients had increased HZ incidence rates,with adjusted incidence rate ratios of 1.35(95%confidence interval[CI],1.26–1.44)and 1.66(95%CI,1.56–1.77),respectively,compared with non-IBD *** analysis indicated increased relative rates of HZ in progressively younger age strata in the UC and CD patients compared with non-IBD *** incidence rates were higher in UC and CD patients who had previously received thiopurines or methotrexate,TNF-inhibitors,or corticosteroids than in UC and CD patients who did not take those ***:UC and CD patients had increased HZ incidence rates compared with patients without IBD,demonstrating the importance of HZ prevention in IBD patients.

关键词： ulcerative colitis Crohn’s disease herpes zoster

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黄连解毒汤对APP/PS1转基因小鼠大脑皮质中TREM2/Akt/GSK3β通路的影响

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中国中药杂志 2024年第7期49卷 1924-1931页

作者：王瑞芳宋军营赵焕东贾亚泉袁永丁蕊王孟菲张振强河南中医药大学中医药科学院河南郑州450046 河南中医药大学第一临床医学院河南郑州450046 河南中医药大学第二临床医学院河南郑州450046

基于“毒损脑络”阿尔茨海默病(Alzheimer′s disease,AD)中医病机,黄连解毒汤治疗AD的机制还不清楚。该研究旨在探讨黄连解毒汤调节髓样细胞触发受体2(triggering receptor expressed on myeloid cells 2,TREM2)/苏氨酸蛋白激酶(protei... 详细信息

基于“毒损脑络”阿尔茨海默病(Alzheimer′s disease,AD)中医病机,黄连解毒汤治疗AD的机制还不清楚。该研究旨在探讨黄连解毒汤调节髓样细胞触发受体2(triggering receptor expressed on myeloid cells 2,TREM2)/苏氨酸蛋白激酶(protein kinase B,Akt)/糖原合酶激酶3β(glycogen synthase kinase 3β,GSK3β)通路改善APP/PS1转基因小鼠认知障碍机制。将9月龄APP/PS1小鼠采用随机数字表法分为模型组,黄连解毒汤低、中、高(2.5、5、10 g·kg^(-1))组和盐酸多奈哌齐0.75 mg·kg^(-1)组,同月龄C57BL/6J小鼠为正常组。连续给药1个月后,采用morris水迷宫检测小鼠的学习记忆能力,苏木素-伊红(HE)染色观察小鼠皮质区神经细胞形态,免疫荧光检测β淀粉样蛋白(β-amyloid,Aβ)_(1-42)、CD86及精氨酸酶1(arginase 1,Arg1)表达情况,实时荧光定量PCR检测小鼠皮质区白细胞介素(interleukin,IL)-1β、IL-6和IL-10 mRNA水平,Western blot法检测小鼠皮质TREM2、磷酸酰肌醇3-激酶(phosphoinositide-3 kinase,PI3K)、Akt、GSK3β和β-连环蛋白(beta-catenin,β-catenin)的蛋白表达。结果表明,与正常组相比,模型组小鼠逃避潜伏期显著延长,目标象限停留时间和穿越平台次数显著减少(Py607)、p-Akt(T308)、p-GSK3β(Ser9)和β-catenin蛋白表达明显下调;与模型组相比,给药组小鼠逃避潜伏期均明显缩短,穿越平台次数和目标象限停留时间明显增加,小鼠皮质区神经元数量增多、核固缩现象改善,Aβ_(1-42)沉积明显减少,IL-1β和IL-6 mRNA和CD86水平显著下降,而IL-10及Arg1显著上升,各给药组小鼠皮质区TREM2、p-PI3K(y607)、p-Akt(T308)、p-GSK3β(Ser9)和β-catenin蛋白表达显著上调。综上所述,黄连解毒汤减少Aβ_(1-42)表达和脑内炎症保护神经元,从而改善APP/PS1小鼠的学习记忆能力,可能与TREM2/Akt/GSK3β信号通路有关。

关键词：阿尔茨海默病黄连解毒汤神经炎症 TREM2 GSK3β

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艾司氯胺酮对发育期大鼠慢性应激后学习记忆功能及海马NMDAR-CaMKⅡ-CREB信号通路的影响

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中华麻醉学杂志 2024年第3期44卷 353-357页

作者：徐桂萍张学雪王洋张宇轩新疆维吾尔自治区人民医院麻醉科新疆麻醉管理临床医学研究中心乌鲁木齐830000 新疆医科大学研究生学院乌鲁木齐830000

目的评价艾司氯胺酮对发育期大鼠慢性应激后学习记忆功能及海马N-甲基-D-天冬氨酸受体(NMDAR)-钙-钙调素依赖性蛋白激酶2型(CaMKⅡ)-环磷酸腺苷反应元件结合蛋白(CREB)信号通路的影响。方法清洁级健康SD大鼠60只,雌雄不拘,7日龄,体质量1... 详细信息

目的评价艾司氯胺酮对发育期大鼠慢性应激后学习记忆功能及海马N-甲基-D-天冬氨酸受体(NMDAR)-钙-钙调素依赖性蛋白激酶2型(CaMKⅡ)-环磷酸腺苷反应元件结合蛋白(CREB)信号通路的影响。方法清洁级健康SD大鼠60只,雌雄不拘,7日龄,体质量10~15 g,采用随机数字表法分为3组(n=20):对照+生理盐水组(CN组)、慢性应激+生理盐水组(NS组)和慢性应激+艾司氯胺酮组(ES组)。采用慢性不可预知性应激方法建立慢性应激模型。应激刺激结束后,ES组腹腔注射艾司氯胺酮10 mg/kg,NS组腹腔注射等容量生理盐水,连续7 d,1次/d。腹腔给药结束后,行y迷宫实验和morris水迷宫实验测定学习记忆功能;取静脉血样,采用ELISA法检测血清皮质醇和ROS浓度;随后麻醉断头取脑,分离海马组织,观察海马CA1区神经元病理学结果,采用Western blot法确定磷酸化NMDAR(p-NMDAR)/NMDAR、磷酸化CaMKⅡ(p-CaMKⅡ)/CaMKⅡ、磷酸化CREB(p-CREB)/CREB表达水平的比值。结果与CN组比较,NS组新臂停留时间缩短,进入新臂次数减少,逃避潜伏期延长,穿越原平台位置次数减少,血清皮质醇和ROS浓度升高,p-NMDAR/NMDAR比值、p-CaMKⅡ/CaMKⅡ比值和p-CREB/CREB比值降低(P<0.05),神经元发生明显病理学损伤;与NS组比较,ES组新臂停留时间延长,进入新臂次数增多,逃避潜伏期缩短,穿越原平台位置次数增多,血清皮质醇和ROS浓度下降,p-NMDAR/NMDAR比值、p-CaMKⅡ/CaMKⅡ比值和p-CREB/CREB比值升高(P<0.05),神经元病理学损伤减轻。结论艾司氯胺酮可改善发育期大鼠慢性应激后学习记忆功能,机制可能与降低氧化应激水平,增强海马NMDAR-CaMKⅡ-CREB信号通路活性有关。

关键词：认知受体,N-甲基-D-天冬氨酸钙-钙调素依赖性蛋白激酶2型 cAMP反应元件结合蛋白质慢性应激艾司氯胺酮

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远端缺血适应外泌体对大鼠心脏骤停后脑损伤的保护作用

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中华急诊医学杂志 2024年第7期33卷 991-998页

作者：翟恒王吉慧陈习张扬胡书群王军彭易根赵宁军燕宪亮苏成磊许铁徐州医科大学附属医院急诊医学科徐州221006 睢宁县人民医院急诊医学科睢宁221200 徐州医科大学第二临床医学院急诊医学实验室徐州221006 南京大学医学院附属鼓楼医院急诊医学科南京210008 南京市江宁医院急诊医学科南京211100 徐州医科大学江苏省卫生应急研究所徐州221006

目的探讨远端缺血适应来源的外泌体对大鼠心脏骤停后神经功能障碍的治疗作用。方法Sprague-Dawley大鼠在经历远端缺血适应后,从血浆中分离出外泌体用作干预药物。36只大鼠被随机分为假手术组、对照组和外泌体组(n=12)。对照组和外泌体... 详细信息

目的探讨远端缺血适应来源的外泌体对大鼠心脏骤停后神经功能障碍的治疗作用。方法Sprague-Dawley大鼠在经历远端缺血适应后,从血浆中分离出外泌体用作干预药物。36只大鼠被随机分为假手术组、对照组和外泌体组(n=12)。对照组和外泌体组大鼠使用窒息法诱导心脏骤停,恢复自主循环后分别静脉输注安慰剂或外泌体悬液(1×1010 Particles)。神经功能缺陷评分、旷场试验、y迷宫和水迷宫用以评估神经功能结果。检测血浆透明质酸(hyaluronic acid,HA)和多配体蛋白聚糖-1(syndecan-1,Sdc-1)水平、检测海马CA1区基质金属蛋白酶2/9(matrix metalloproteinase-2/9,MMP-2/9)的表达水平。结果在经历远端缺血适应后,大鼠血浆中外泌体含量较正常大鼠升高。和对照组相比,外泌体组大鼠行为学实验明显改善,表现为水平运动距离增加(5.86±2.89 vs.17.53±5.51,P<0.05)、自发交替正确率升高(13.29±15.07 vs.42.63±10.25,P<0.05)、逃避潜伏期缩短(25.83±8.54 vs.13.49±4.55,P<0.05)。复苏后24 h的血浆HA和Sdc-1水平明显降低(HA:26.34±9.83 vs.14.84±6.26,P<0.05;Sdc-1:0.05±0.03 vs.0.02±0.02,P<0.05),同时海马组织中MMP-2/9水平明显降低。结论从经历远端缺血适应的大鼠血浆中提取出的外泌体能够改善大鼠心脏骤停后神经功能障碍,其机制可能与MMP-2/9的减少以内皮糖萼降解减少有关。

关键词：远端缺血适应外泌体心脏骤停神经保护糖萼透明质酸多配体蛋白聚糖-1 基质金属蛋白酶2 基质金属蛋白酶9

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The role of land use on the local climate and air quality during calm inter-monsoon in a tropical city

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Geoscience Frontiers 2019年第2期10卷 405-415页

作者： M.C.G.Ooi A.Chan M.J.Ashfold M.y.Oozeer K.I.morris S.S.K.Kong Department of Atmospheric Science "Central University" Department of Civil Engineering University of Nottingham Malaysia Campus School of Environmental and Geographical Sciences University of Nottingham Malaysia Campus Department of Geography and Environmental Management University of Waterloo Center of Excellence for Sustainable Innovation and Research Initiative (CESIRI) Department of Mechanical Engineering Ashesi University College

The modification of land use is known to be a major climate change driver to the local warming and air quality in cities. Despite the reduction of NOx over the years, the Selangor state has captured a higher level of O_3 in year 2011. The measurement result has shown that the surge in O_3 level was attributed to the reduction of NO_x/NMHC ratio. This paper hence attempted to identify the role of land use change from 1999 to 2011 on the ground ozone air quality in the tropical urban conurbation, Greater Kuala Lumpur(GKL), Selangor, Malaysia. With the state-of-the-art chemical weather prediction tool, WRFChem, the external synoptic factors and emission inventory were controlled when comparing the chronological land use changes. The results showed that the urban-induced temperature and wind bias in the tropical region has induced stronger wind to disperse the NO_x and carries the TVOC from the suburban to the downwind urban region. The reduction of NO_x/TVOC has gradually shifted towards the optimum O_3 formation regime in 2011. The formation of highly concentrated ozone becomes more sensitive to the increment of TVOC as the NO_x level reduces in the urban. This highlights the essential involvement of TVOC in the ozone formation in lieu of the NOx reduction in the tropical city, a region with growing emitter of reactive biogenic ozone precursors.

关键词： Land use change Urban Ground ozone TVOC WRF-Chem Tropics

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Beclin 1-Vps34 complex architecture： Understanding the nuts and bolts of therapeutic targets

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Frontiers in Biology 2015年第5期10卷 398-426页

作者： Deanna H. morris Calvin K. yip yi Shi Brian T. Chait Qing Jun wang Department of Molecular and Cellular Biochemistry University of Kentucky Lexington KY 40536 USA Department of Biochemistry and Molecular Biology The University of British Columbia Vancouver BC V6TIZ3 Canada Laboratory of Mass Spectrometry and Gaseous Ion Chemistry The Rockefeller University New York NY 10065 USA Department of Toxicology and Cancer Biology University of Kentucky Lexington KY 40536 USA Markey Cancer Center University of Kentucky Lexington KY 40536 USA

Autophagy is an important lysosomal degradation pathway that aids in the maintenance of cellular homeostasis by breaking down and recycling intracellular contents. Dysregulation of autophagy is linked to a growing number of human diseases. The Beclin 1-Vps34 protein-protein interaction network is critical for autophagy regulation and is therefore essential to cellular integrity. Manipulation of autophagy, in particular via modulation of the action of the Beclin I-Vps34 complexes, is considered a promising route to combat autophagy-related diseases. Here we summarize recent findings on the core components and structural architecture of the Beclin 1-Vps34 complexes, and how these findings provide valuable insights into the molecular mechanisms that underlie the multiple functions of these complexes and for devising therapeutic strategies.

关键词： Beclin 1 Vps34 Nrbf2 complex structure CX-MS EM inhibitor drag design

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基于网络药理学、分子对接与动物实验探究百合地黄汤治疗阿尔茨海默病的作用机制

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中国现代应用药学 2024年第8期41卷 1027-1037页

作者：贾铷周小如陈燕张淑玲赖兆铠王玉露福建中医药大学福州350122

目的基于网络药理学、分子对接与动物实验探究百合地黄汤治疗阿尔茨海默病的作用机制。方法利用TCMSP数据库预测百合地黄汤的活性成分及靶点;在GeneCards、OMIM、DRUGBANK等数据库检索阿尔茨海默病靶点,利用Cytoscape 3.8.0建立交集... 详细信息

目的基于网络药理学、分子对接与动物实验探究百合地黄汤治疗阿尔茨海默病的作用机制。方法利用TCMSP数据库预测百合地黄汤的活性成分及靶点;在GeneCards、OMIM、DRUGBANK等数据库检索阿尔茨海默病靶点,利用Cytoscape 3.8.0建立交集靶点网络,GO富集及KEGG通路分析在Metascape数据库进行;运用AutoDock vina软件进行分子对接,并使用PyMOL等软件进行可视化分析;将小鼠分为空白组、模型组、咯利普兰组和百合地黄汤低、中、高剂量组,给药14 d后各组小鼠进行神经行为学评分,检测脑组织内相关蛋白表达,使用ELISA和Western blotting检测关键基因c AMP、PKA、p-CREB、BDNF的蛋白表达。最后通过呕吐实验观察百合地黄汤的不良反应。结果获得百合地黄汤活性成分13种,作用于阿尔茨海默病靶点39个,与PRKACA关系密切。动物实验结果表明,与正常组比较,模型组小鼠对新物体的辨认率明显下降,新位置的物体辨认率有下降趋势,y迷宫中自主交替的反应率明显下降,morris水迷宫中逃避潜伏期明显延长、平台所在象限停留时间和经过平台次数显著减少,且脑中cAMP、PKA、pCREB、BDNF蛋白表达下降,而百合地黄汤组与咯利普兰组能够逆转上述行为学以及蛋白指标的变化。在呕吐实验中,咯利普兰组麻醉苏醒时间显著延长,百合地黄汤组无明显影响。结论百合地黄汤治疗阿尔茨海默病的作用机制可能与其影响c AMP-PKA以及调控cAMP-PKA-CREB-BDNF信号通路有关,且不良反应较咯利普兰轻。

关键词：百合地黄汤东莨菪碱阿尔茨海默病行为学试验网络药理学

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