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Effects of natural-cerebrolysin-containing serum on neurotoxicity and synaptogenesis in amyloid-beta 1-40-induced Alzheimer's disease in vitro models 被引量:1
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作者 Yinghong Li Zhengzhi Wu +3 位作者 Andrew C. J. HuangO Ming Li XiaoLi Zhang Jiguo Wang 《Neural Regeneration Research》 SCIE CAS CSCD 2009年第2期85-91,共7页
BACKGROUND: Neuronal loss, synapse mutilation, and increasing malnourished axons are pathologically related to Alzheimer's disease. Microtubule-associated protein 2 (MAP2) is of importance for neuronal, axonal, an... BACKGROUND: Neuronal loss, synapse mutilation, and increasing malnourished axons are pathologically related to Alzheimer's disease. Microtubule-associated protein 2 (MAP2) is of importance for neuronal, axonal, and dendritic generation, extension, and stabilization, as well as for the regulation of synaptic plasticity. OBJECTIVE: To investigate the antagonistic effects of natural-cerebrolysin-containing serum on beta amyloid protein 1-40 (Aβ1-40)-induced neurotoxicity from the standpoints of cell proliferation, synaptogenesis, and cytoskeleton formation (MAP2 expression). DESIGN, TIME AND SETTING: A paralleled, controlled, neural cell, and molecular biology experiment was performed at the Institute of Integrated Chinese and Western Medicine, Shenzhen Hospital, Southern Medical University between February 2006 and April 2008. MATERIALS: PC12 cells, derived from the rat central nervous system, were purchased from Shanghai Institute of Cell Biology, Chinese Academy of Sciences, China. A β1-40 was provided by Sigma, USA. Natural-cerebrolysin was provided by Shenzhen Institute of Integrated Chinese and Western Medicine, China. The natural-cerebrolysin was predominantly composed of Renshen (Radix Ginseng), Tianma (Rhizoma Gastrodiae), and Yixingye (Ginkgo Leaf) in a proportion of 1:2:2. Following conventional water extraction technology, an extract (1:20) was prepared. Each gram of extract equaled 20 grams of crude drug. In a total of 12 adult male New Zealand rabbits, six underwent intragastric administration of natural-cerebrolysin extract for 1 month to prepare natural-cerebrolysin-containing serum, and the remaining six rabbits received intragastric administration of physiological saline to prepare normal blank serum. METHODS: An AIzheimer's disease in vitro model was induced in PC12 cells using Aβ1-40. The cells were incubated with varying doses of natural-cerebrolysin-containing serum (2.5%, 5%, and 10%). Normal blank serum-treated PC12 cells served as a blank control group. MAIN OUTCOME MEASURES: Through the use of inverted phase contrast microscope, cell morphology and neurite growth were observed, neurite length was measured, and the percentage of neurite-positive cells was calculated. Cell proliferation rate was determined by MTT assay, and MAP 2 expression was detected by fluorescent immunocytochemistry. RESULTS: Following Aβ1-40 treatments, some PC12 cells were apoptotic/dying, and only a few short neurites were observed. Following interventions with natural-cerebrolysin-containing serum, the PC12 cells proliferated, there was an increased number of neurites, and neurite length was enhanced. After middle- and high-dose natural-cerebrolysin treatments, the percentage of neurite-positive cells, as well as the average length of neurites, was significantly greater than the normal blank serum-treated PC12 cells (P 〈 0.05 or P 〈 0.01). Compared with the blank control group, MAP2 expression in the Aβ1-40-treated PC12 cells was significantly inhibited, and the cell proliferation rate was significantly decreased (P 〈 0.01). Following incubations with natural-cerebrolysin-containing serum, MAP2 expression and cell proliferation rate in the PC12 cells were significantly increased in a dose-dependent manner, compared with treatments with blank control serum (P 〈 0.05 or P 〈 0.01 ). CONCLUSION: Natural-cerebrolysin exhibited antagonistic effects on neurotoxicity in Aβ1-40 induced Alzheimer's disease in vitro models. These effects were likely related to cell proliferation and the upregulation of intracellular MAP2 expression. 展开更多
关键词 natural-cerebrolysin Alzheimer's disease in vitro model NEUROTOXICITY neuroprotective effect amyloid beta protein 1-40
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Effects of natural cerebrolysin on protective proteins and pro-apoptotic molecules in mesenchymal stem cells following beta-amyloid peptide1-40-induced endoplasmic reticulum stress 被引量:1
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作者 Yinghong Li Zhengzhi Wu +4 位作者 Ming Li Xiaoli Zhang Min Yang Manyin Chen Andrew C. J.Huang O 《Neural Regeneration Research》 SCIE CAS CSCD 2009年第12期986-993,共8页
BACKGROUND: Studies have demonstrated that β-amyloid peptide (Aβ), a characteristic pathological product of Alzheimer's disease (AD), results in neuronal endoplasmic reticulum stress (ERS). However, the mech... BACKGROUND: Studies have demonstrated that β-amyloid peptide (Aβ), a characteristic pathological product of Alzheimer's disease (AD), results in neuronal endoplasmic reticulum stress (ERS). However, the mechanisms of traditional Chinese medicine against ERS in AD are poorly understood. OBJECTIVE: To measure expression levels of protective proteins (GRP78 and GRP94) of ER molecular partners and pro-apoptotic Caspase-12 ER membrane expression following application of traditional Chinese medicine natural cerebrolysin (NC) to treat Aβ1-40-induced ERS. DESIGN, TIME AND SETTING: A parallel-controlled study was performed at the Institute of Integrated Western and Traditional Chinese Medicine, Shenzhen Hospital of Southern Medical University between September 2006 and November 2008. MATERIALS: Sprague Dawley male rats, 6-8 weeks old, were used to harvest tibial and femoral bone marrow. Isolation and purification of mesenchymal stem cells (MSCs) were established from the whole bone marrow by removing non-adherent cells in primary and passage cultures. Aβ1-40 was provided by Sigma, USA. NC was provided by Shenzhen Institute of Integrated Chinese and Western Medicine, China. NC was predominantly composed of Renshen (Radix Ginseng), Tianma (Rhizoma Gastrodiae), and Yinxingye (Ginkgo Leaf) in a proportion of 1 : 2: 2. Following conventional water extraction technology, an extract (1 : 20) was prepared. Six adult, male, New Zealand rabbits underwent intragastric administration of NC extract (0.976 g/kg per day) for 1 month to prepare NC-positive serum, and the remaining 6 rabbits received intragastric administration of physiological saline to prepare normal blank serum. METHODS: A total of 500 nmol/L Aβ1-40 was used to establish ERS models of primary cultured MSCs. AD cell models were incubated with different doses of NC-positive serum (2.5%, 5%, and 10%). MSCs treated with normal blank serum served as normal blank controls. MAIN OUTCOME MEASURES: Reverse transcription-polymerase chain reaction and fluorescent immunocytochemistry were respectively used to measure mRNA and protein expression levels of GRP78, GRP94, and Caspase-12 in MSCs. RESULTS: Following Aβ1-40 exposure, mRNA and protein expression levels of GRP78 and GRP94, as well as Caspase-12, significantly increased (P 〈 0.05), suggesting successful establishment of ERS models. Following NC-positive serum application, mRNA and protein expression levels of GRP78 and GRP94 in MSCs significantly increased (P 〈 0.05 or P 〈 0.01). However, mRNA and protein expression levels of Caspase-12 significantly decreased (P 〈 0.05, or P 〈 0.01) compared with the ERS model group. These effects were dose-dependent. CONCLUSION: NC downregulated Caspase-12 expression and upregulated GRP78 and GRP94 expression in MSCs in a dose-dependent manner under the state of Aβ1-40-induced ERS. 展开更多
关键词 endoplasmic reticulum stress amyloid beta protein 1-40 Alzheimer's Disease natural cerebrolysin protective effect mesenchymal stem cells
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Inhibitory effects of scorpion venom heat-resistant protein on neurotoxicity of exogenous amyloid beta peptide 1-40
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作者 Shengbo Yu Jin Gong +5 位作者 Haibin Gao Yanyan Chi Yan Peng Hongjin Sui Jie Zhao Wanqin Zhang 《Neural Regeneration Research》 SCIE CAS CSCD 2009年第12期1030-1036,共7页
BACKGROUND: Studies have shown that scorpion venom heat-resistant protein (SVHRP) exhibits protective effects on primary cultured hippocampal neurons. OBJECTIVE: To determine the effects of SVHRP on astrocyte acti... BACKGROUND: Studies have shown that scorpion venom heat-resistant protein (SVHRP) exhibits protective effects on primary cultured hippocampal neurons. OBJECTIVE: To determine the effects of SVHRP on astrocyte activity and synaptic density in the hippocampus induced by amyloid β peptide 1-40 (Aβ1-40) neurotoxicity. DESIGN, TIME AND SETTING: The randomized, controlled, animal experiment was performed at the Central Laboratory, the Laboratory of Human Anatomy, and the Laboratory of Physiology, in Dalian Medical University between March 2006 and June 2008. MATERIALS: Aβ1-40 was provided by Biosource, USA; SVHRP was a patented biological product of Dalian Medical University (No. ZL01 1 06166.9). METHODS: A total of 27 healthy, 2-month-old, male SD rats were randomly assigned to 3 groups: control, Aβ, and SVHRP, with 9 rats in each group. Alzheimer's disease was simulated with 10 μg Aβ1-40 bilaterally injected into the hippocampus of the Aβ and SVHRP groups. The control group was injected with 2 μL 0.05% trifluoroacetic acid. One day following model establishment, the SVHRP group received an intraperitoneal injection of 2 μg/100 g SVHRP, while the control group and Aβ group received 0.5 mL/100 g tri-distilled water, once per day, for 10 consecutive days. MAIN OUTCOME MEASURES: At 16 days following model establishment, synaptophysin (p38) expression in CA1-CA4 regions of the rat hippocampus was determined by immunohistochemistry. Glial fibrillary acidic protein (GFAP) expression surrounding the hippocampal Aβ1-40 injected area was also detected. At 11 days following model establishment, escape latency, swimming time, and distance to target quadrant were measured using the Morris water maze. RESULTS: Compared with the control group, the Aβ group exhibited notably reduced p38 expression (P 〈 0.05) and notably increased GFAP expression in the rat hippocampus (P 〈 0.05). Water maze results demonstrated that escape latency was prolonged (P 〈 0.05), and swimming time and distance to the target quadrant were shortened in the Aβ group. Compared with the Aβ group, the SVHRP group exhibited notably increased p38 expression (P 〈 0.05) and notably decreased GFAP expression in the rat hippocampus (P 〈 0.05). Water maze results demonstrated that escape latency was significantly reduced (P 〈 0.05), and swimming time and distance to the target quadrant were significantly prolonged. CONCLUSION: SVHRP inhibited exogenous Aβ1-40-induced astrocyte activation and synaptic density decline in the rat hippocampus. Place navigation and spatial searching results showed that SVHRP blocked Aβ1-40-induced impaired learning and memory. 展开更多
关键词 amyloid β peptide 1-40 Alzheimer's disease scorpion venom heat-resistant protein Morris water maze SYNAPTOPHYSIN glial fibrillary acidic protein
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Hyperoside protects the blood-brain barrier from neurotoxicity of amyloid beta 1–42 被引量:5
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作者 Chen-Yang Liu Kuan Bai +2 位作者 Xiao-Hui Liu Li-Mi Zhang Gu-Ran Yu 《Neural Regeneration Research》 SCIE CAS CSCD 2018年第11期1974-1980,共7页
Mounting evidence indicates that amyloid β protein(Aβ) exerts neurotoxicity by disrupting the blood-brain barrier(BBB) in Alzheimer's disease. Hyperoside has neuroprotective effects both in vitro and in vivo ag... Mounting evidence indicates that amyloid β protein(Aβ) exerts neurotoxicity by disrupting the blood-brain barrier(BBB) in Alzheimer's disease. Hyperoside has neuroprotective effects both in vitro and in vivo against Aβ. Our previous study found that hyperoside suppressed Aβ1-42-induced leakage of the BBB, however, the mechanism remains unclear. In this study, bEnd.3 cells were pretreated with 50, 200, or 500 μM hyperoside for 2 hours, and then exposed to Aβ1-42 for 24 hours. Cell viability was determined using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Flow cytometry and terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling assay were used to analyze cell apoptosis. Western blot assay was carried out to analyze expression levels of Bax, Bcl-2, cytochrome c, caspase-3, caspse-8, caspase-9, caspase-12, occludin, claudin-5, zonula occludens-1, matrix metalloproteinase-2(MMP-2), and MMP-9. Exposure to Aβ1-42 alone remarkably induced bEnd.3 cell apoptosis; increased ratios of cleaved caspase-9/caspase-9, Bax/Bcl-2, cleav ed caspase-8/caspase-8, and cleaved caspase-12/caspase-12; increased expression of cytochrome c and activity of caspase-3; diminished levels of zonula occludens-1, claudin-5, and occludin; and increased levels of MMP-2 and MMP-9. However, hyperoside pretreatment reversed these changes in a dose-dependent manner. Our findings confirm that hyperoside alleviates fibrillar Aβ1-42-induced BBB disruption, thus offering a feasible therapeutic application in Alzheimer's disease. 展开更多
关键词 nerve regeneration Alzheimer's disease amyloid beta 1-42 blood-brain barrier bEnd.3 cells tight junction proteins HYPEROSIDE ANTI-APOPTOSIS neural regeneration
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远志皂苷对β淀粉样蛋白片段1-40诱导PC12细胞凋亡的抑制作用 被引量:19
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作者 杨贤志 陈勤 +2 位作者 陈庆林 金蓓蓓 叶海燕 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2013年第3期379-384,共6页
目的探讨远志皂苷抑制β淀粉样蛋白片段1-40(Aβ1-40)诱导的PC12细胞凋亡的作用机制。方法采用聚集状的Aβ1-40 25μmol·L-1诱导PC12细胞凋亡,然后将处理后的PC12细胞分为Aβ1-40模型组和远志皂苷50,100和200μmol·L-1组,同... 目的探讨远志皂苷抑制β淀粉样蛋白片段1-40(Aβ1-40)诱导的PC12细胞凋亡的作用机制。方法采用聚集状的Aβ1-40 25μmol·L-1诱导PC12细胞凋亡,然后将处理后的PC12细胞分为Aβ1-40模型组和远志皂苷50,100和200μmol·L-1组,同时设正常细胞对照组。采用MTT比色法检测细胞存活率;膜联蛋白-Ⅴ和PI双染法检测细胞凋亡率;免疫细胞化学法检测细胞凋亡基因Bcl-2和Bax及细胞色素c(Cyt c)表达阳性的细胞百分率;Western印迹法检测PC12细胞中Cyt c的表达水平。结果与正常对照组比较,Aβ1-40模型组PC12细胞的存活率明显降低(P<0.01),为(31±7)%;Bcl-2阳性表达细胞率降低(P<0.01),为(23.9±1.9)%;Bax和Cyt c阳性表达细胞率升高(P<0.01),分别为(79.0±3.7)%和(49.2±3.6)%,Bcl-2/Bax阳性表达细胞比值为0.30。与模型对照组比较,远志皂苷50,100和200μmol·L-1作用24 h后,细胞存活率分别升高至(51±13)%,(64±7)%和(84±10)%(P<0.01);Bcl-2阳性率升高至(38.7±0.9)%,(53.7±1.6)%和(60.3±0.8)%(P<0.01),Bax阳性率分别降低为(60.8±1.9)%,(41.5±2.2)%和(32.7±1.4)%(P<0.01),Bcl-2/Bax比值亦分别上升为0.64,1.29和1.84;Cyt c阳性率分别降低至(45.4±3.4)%,(30.2±2.2)%和(27.5±1.0)%(P<0.05,P<0.01)。与正常对照组比较,模型组PC12细胞凋亡率和Cyt c蛋白表达水平亦明显升高(P<0.01);远志皂苷50,100和200μmol·L-1作用24h,PC12细胞凋亡率和Cyt c表达水平较模型组均降低(P<0.01)。结论远志皂苷对Aβ1-40诱导的PC12细胞凋亡具有明显的抑制作用,其作用机制可能是抑制Bax和Cyt c表达,增加Bcl-2表达和Bcl-2/Bax比值,从而阻断内源性细胞凋亡通路。 展开更多
关键词 远志皂苷 β淀粉样蛋白片段1-40 PC12细胞 细胞凋亡 细胞色素C
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全麻老年患者围术期血浆β-淀粉样蛋白1-40的变化及其意义 被引量:5
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作者 范隆 薛纪秀 +2 位作者 王克杰 魏立民 于克荣 《临床麻醉学杂志》 CAS CSCD 2008年第10期843-845,共3页
目的观察全麻老年患者围术期血浆β-淀粉样蛋白1-40[Aβ(1-40)]水平的变化,探讨其与手术后认知功能障碍(POCD)的关系。方法40例择期开腹手术患者按照年龄分为两组:青年组(20例,年龄在20~50岁之间);老年组(20例,年龄≥65岁)。分别在手... 目的观察全麻老年患者围术期血浆β-淀粉样蛋白1-40[Aβ(1-40)]水平的变化,探讨其与手术后认知功能障碍(POCD)的关系。方法40例择期开腹手术患者按照年龄分为两组:青年组(20例,年龄在20~50岁之间);老年组(20例,年龄≥65岁)。分别在手术前一天和手术后24 h进行简易智能量表(MMSE)评分。于手术前(T1)、手术开始后2 h(T2)、4 h(T3)、24 h(T4)采集静脉血标本,用酶联免疫吸附(ELISA)法测定血浆Aβ(1-40)。结果与手术前相比,老年组手术后MMSE评分明显降低;青年组差异无统计学意义。老年组血浆Aβ(1-40)T1~T4各时点均高于青年组(P<0.05),且在T2~T4时均显著高于T1时(P<0.05)。结论老年人血浆Aβ(1-40)基础水平较高且手术开始后24 h持续维持于较高水平,可能是老年人POCD发生率高的原因之一。 展开更多
关键词 β-淀粉样蛋白140 术后认知功能障碍 临床分析 治疗方法
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普罗布考对脑梗死合并认知功能障碍患者Aβ_(1-40)和MMP-9的影响 被引量:8
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作者 董晓柳 张利 +2 位作者 高秋燕 徐士军 张秀清 《中国循证心血管医学杂志》 2016年第7期881-883,886,共4页
目的 探讨普罗布考对脑梗死合并认知功能障碍患者β淀粉样蛋白1-40(Aβl-40)和基质金属蛋白酶-9(MMP-9)的影响。方法 选择2012年12月~2014年10月于唐山市人民医院诊治的脑梗死合并认知功能障碍患者138例,男性81例,女性57例,年... 目的 探讨普罗布考对脑梗死合并认知功能障碍患者β淀粉样蛋白1-40(Aβl-40)和基质金属蛋白酶-9(MMP-9)的影响。方法 选择2012年12月~2014年10月于唐山市人民医院诊治的脑梗死合并认知功能障碍患者138例,男性81例,女性57例,年龄52~74岁。随机分为两组,对照组和观察组,各69例。对照组采用阿托伐他汀治疗,观察组采用阿托伐他汀联合普罗布考治疗,疗程6个月。比较两组患者治疗前后的神经功能状况、认知功能状况、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、Aβl-40和MMP-9改变情况。结果 治疗6个月后,两组患者较治疗前NIHSS评分均显著降低,MMSE评分、MoCA评分均显著增加,差异有统计学意义(P均<0.05)。观察组治疗后NIHSS评分明显低于对照组,MMSE评分、MoCA评分均明显高于对照组,差异均具有统计学意义(P均<0.05)。治疗后,两组患者TC、TG、LDL-C均显著降低,HDL-C均显著增加,差异有统计学意义(P均<0.05)。观察组治疗后TC、TG、LDL-C均明显低于对照组,HDL-C明显高于对照组,差异均具有统计学意义(P均<0.05)。治疗6个月后,两组患者Aβl-40、MMP-9均显著降低,观察组患者治疗后Aβl-40、MMP-9均明显低于对照组,数值为[(130.27±16.93)pg/ml vs.(154.17±20.41)pg/ml],[(196.04±43.28)mg/L vs. (256.37±51.23)mg/L],差异均具有统计学意义(P均<0.05)。观察组患者不良反应发生率与对照组相比,差异无统计学意义(P>0.05)。结论 普罗布考可明显改善脑梗死合并认知功能障碍患者的神经功能状况和认知功能状况,调节血脂,能降低Aβl-40和MMP-9水平,具有较高的安全性。 展开更多
关键词 普罗布考 脑梗死 认知功能障碍 β淀粉样蛋白40 基质金属蛋白酶-9
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β淀粉样肽_(1-40)通过激活caspase-3诱导大鼠皮层神经元凋亡 被引量:2
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作者 陈丽敏 陈晓春 +1 位作者 朱元贵 周宜灿 《解剖学报》 CAS CSCD 北大核心 2003年第4期379-383,共5页
目的 探讨半胱氨酸蛋白酶caspase 3在 β淀粉样肽1 4 0 (β AP1 4 0 )诱导大鼠皮层神经元凋亡中的可能作用。 方法 用 β AP1 4 0 诱导神经元凋亡 ,同时检测caspase 3活力和caspase 3活性片段及caspase 3mRNA的表达水平。 结果 ... 目的 探讨半胱氨酸蛋白酶caspase 3在 β淀粉样肽1 4 0 (β AP1 4 0 )诱导大鼠皮层神经元凋亡中的可能作用。 方法 用 β AP1 4 0 诱导神经元凋亡 ,同时检测caspase 3活力和caspase 3活性片段及caspase 3mRNA的表达水平。 结果  4 0mg·L- 1 的凝聚态 β AP1 4 0 诱导大鼠皮层神经元凋亡过程中 ,caspase 3活力和caspase 3mRNA的表达水平均有明显增高 (P <0 0 1) ;特异性的caspase 3抑制剂Ac DEVD CHO对caspase 3的激活和皮层神经元细胞凋亡均有明显的阻断作用。 结论 caspase 3可能是 β AP1 4 0 展开更多
关键词 β淀粉样肽1-40 CASPASE-3 诱导 大鼠 皮层神经元 凋亡
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β淀粉样蛋白1-40与老年患者颌面外科手术后并发谵妄的关系 被引量:1
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作者 郁葱 张青 +2 位作者 陈思路 罗玉琳 肖水生 《华西口腔医学杂志》 CAS CSCD 北大核心 2010年第5期498-501,共4页
目的观察老年颌面外科手术患者全身麻醉后术后谵妄(PD)的患病率,研究血浆β淀粉样蛋白1-40(Aβ1-40)与PD的关系。方法选择50例颌面外科手术患者,按照年龄分为T组(30例,年龄62~78岁)和C组(20例,年龄20~60岁),2组均采用静吸复合麻醉,以... 目的观察老年颌面外科手术患者全身麻醉后术后谵妄(PD)的患病率,研究血浆β淀粉样蛋白1-40(Aβ1-40)与PD的关系。方法选择50例颌面外科手术患者,按照年龄分为T组(30例,年龄62~78岁)和C组(20例,年龄20~60岁),2组均采用静吸复合麻醉,以谵妄评定量表1998年修订版(DRS-R-98)来诊断和评估PD发生状况,记录术前(T0),术后24 h(T1)、48 h(T2)、72 h(T3)、96 h(T4)的DRS-R-98评分;并测定Aβ1-40质量浓度。结果 T组患者PD的患病率为20.0%。T组Aβ1-40质量浓度在T0、T1、T2、T3时段明显高于C组(P<0.01),T组和C组Aβ1-40质量浓度在T1和T2时段明显高于同组T0时段(P<0.05)。T组在T3和T4时段的DRS-R-98评分明显高于同组T1时段和C组(P<0.01)。结论 Aβ1-40在全身麻醉后持续升高可能是老年患者发生PD的重要原因之一。 展开更多
关键词 谵妄 Β淀粉样蛋白1-40 谵妄评定量表修订版
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脑低灌注患者检测血浆β淀粉样蛋白1-40和1-42水平的价值 被引量:1
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作者 林森 赵连东 +2 位作者 周永 赵颖 张新勇 《现代中西医结合杂志》 CAS 2011年第28期3523-3525,共3页
目的探讨脑低灌注(CHP)患者血浆中β淀粉样蛋白1-40(Aβ1-40)和Aβ1-42测定的临床价值。方法以ELISA法,检测44例经CT血管成像确定狭窄程度<70%的脑低灌注患者和40例同期对照(HC)者的血浆Aβ1-40和Aβ1-42水平。结果 CHP组血浆Aβ1-40... 目的探讨脑低灌注(CHP)患者血浆中β淀粉样蛋白1-40(Aβ1-40)和Aβ1-42测定的临床价值。方法以ELISA法,检测44例经CT血管成像确定狭窄程度<70%的脑低灌注患者和40例同期对照(HC)者的血浆Aβ1-40和Aβ1-42水平。结果 CHP组血浆Aβ1-40和Aβ1-40/Aβ1-42比值明显高于HC组,而Aβ1-42水平则明显低于HC组。Aβ1-40和Aβ1-42是与血管狭窄相关的独立因素(R2=0.923,P<0.01)。结论脑缺血损伤导致CHP患者血浆Aβ1-40升高和Aβ1-42降低,对其进行检测具有一定的临床诊断价值。 展开更多
关键词 脑低灌注 β-淀粉样蛋白140 β-淀粉样蛋白1—42
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大鼠海马立体定向注射Aβ 1-40建立阿尔茨海默病动物模型 被引量:13
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作者 朱飞奇 马英 钱采韵 《郧阳医学院学报》 2008年第2期106-108,共3页
目的:研究大鼠双侧海马立体定向注射Aβ1-40建立阿尔茨海默病动物模型的方法。方法:通过Mor-ris水迷宫试验观察大鼠双侧海马立体定向注射Aβ1-40对其记忆能力的影响;以及改良刚果红染色法检测Aβ1-40注射后大鼠海马组织的病理学变化。结... 目的:研究大鼠双侧海马立体定向注射Aβ1-40建立阿尔茨海默病动物模型的方法。方法:通过Mor-ris水迷宫试验观察大鼠双侧海马立体定向注射Aβ1-40对其记忆能力的影响;以及改良刚果红染色法检测Aβ1-40注射后大鼠海马组织的病理学变化。结果:大鼠双侧海马立体定向注射Aβ1-40显著导致大鼠空间记忆能力损害,注射点周围有大量的胶质细胞活化。结论:大鼠双侧海马立体定向注射Aβ1-40是一种比较理想的研究炎症在AD发病机理中的动物模型。 展开更多
关键词 阿尔茨海默病 大鼠模型 140
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Effect of Panax notoginseng saponins on the expression of beta-amyloid protein in the cortex of the parietal lobe and hippocampus, and spatial learning and memory in a mouse model of senile dementia 被引量:9
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作者 Zhenguo Zhong Dengpan Wu Liang Lu Jinsheng Wang Wenyan Zhang Zeqiang Qu 《Neural Regeneration Research》 SCIE CAS CSCD 2008年第12期1297-1303,共7页
BACKGROUND: The pharmacological actions of Panax notoginseng saponins (PNS) lie in removing free radicals, anti-inflammation and anti-oxygenation. It can also improve memory and behavior in rat models of Alzheime... BACKGROUND: The pharmacological actions of Panax notoginseng saponins (PNS) lie in removing free radicals, anti-inflammation and anti-oxygenation. It can also improve memory and behavior in rat models of Alzheimer's disease. OBJECTIVE: Using the Morris water maze, immunohistochemistry, real-time PCR and RT-PCR, this study aimed to measure improvement in spatial learning, memory, expression of amyloid precursor protein (App) and β -amyloid (A β ), to investigate the mechanism of action of PNS in the treatment of AD in the senescence accelerated mouse-prone 8 (SAMP8) and compare the effects with huperzine A. DESIGN, TIME AND SETTING: A completely randomized grouping design, controlled animal experiment was performed in the Center for Research & Development of New Drugs, Guangxi Traditional Chinese Medical University from July 2005 to April 2007. MATERIALS: Sixty male SAMP8 mice, aged 3 months, purchased from Tianjin Chinese Traditional Medical University of China, were divided into four groups: PNS high-dosage group, PNS low-dosage group, huperzine A group and control group. PNS was provided by Weihe Pharmaceutical Co., Ltd. (batch No.: Z53021485, Yuxi, Yunan Province, China). Huperzine A was provided by Zhenyuan Pharmaceutical Co., Ltd. (batch No.: 20040801, Zhejiang, China). METHODS: The high-dosage group and low-dosage group were treated with 93.50 and 23.38 mg/kg PNS respectively per day and the huperzine A group was treated with 0.038 6 mg/kg huperzine A per day, all by intragastric administration, for 8 consecutive weeks. The same volume of double distilled water was given to the control group. MAIN OUTCOME MEASURES: After drug administration, learning and memory abilities were assessed by place navigation and spatial probe tests. The recording indices consisted of escape latency (time-to-platform), and the percentage of swimming time spent in each quadrant. The number of A β 1-40, A β 1-42 and App immunopositive neurons in the brains of SAMP8 mice was analyzed by immunohistochemistry. The mRNA content ofApp, tau, acetylcholinesterase, and synaptophysin (Syp) was tested by real time PCR and RT-PCR. RESULTS: The PCR results show that PNS can downregulate the expression of the App gene and upregulate the expression of the Syp gene in the parietal cortex and hippocampus of SAMP8 mice. The therapeutic effects of the PNS high-dosage group were greater than those of the PNS low-dosage group and the huperzine A group (P 〈 0.05). The results of the Morris water maze and immunohistochemistry indicated that PNS can improve the capacity for spatial learning and memory in SAMP8 mice, and reduce the content of A β 1-40, A β 1-42 and expression of App in the brains of SAMP8 mice. The therapeutic effects of the PNS high-dosage group were greater than that of the PNS low-dosage group and the huperzine A group (P 〈 0.05). CONCLUSION: These results support the hypothesis that PNS plays a therapeutic and protective role on the pathological lesions and learning dysfunction of Alzheimer's disease. The therapeutic effects of PNS for Alzheimer's disease are possibly achieved through downregulating the expression of the App gene and upregulating the expression of the Syp gene. The therapeutic effects of PNS are dose-dependent and are greater than the effect of huperzine A. 展开更多
关键词 Alzheimer's disease Panax notoginseng saponins learning and memory β -amyloid precursor protein 1-40 β -amyloid precursor protein 1-42 amyloid β -peptide SYNAPTOPHYSIN senescence accelerated mouse-prone 8
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脑血管病的研究进展
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作者 谢曦 蔡志友 +2 位作者 王启征 刘芮芳 赵宇 《国际医药卫生导报》 2024年第13期2114-2118,I0003,共6页
脑血管病是我国致死率和致残率位居首位的疾病,研究脑血管病的主要目标是降低致死率,减少致残率,提高人们生活质量。通过对新型神经组织成像在脑血管病诊断中的研究可以提高诊断效率及精准度,对新型药物的开发和新治疗方案的研究可以缩... 脑血管病是我国致死率和致残率位居首位的疾病,研究脑血管病的主要目标是降低致死率,减少致残率,提高人们生活质量。通过对新型神经组织成像在脑血管病诊断中的研究可以提高诊断效率及精准度,对新型药物的开发和新治疗方案的研究可以缩短病程及促进恢复,对脑血管病预防措施的研究可以指导人们的健康生活方式。本文就近年来的脑血管病影像研究进展、新型药物及新治疗方案的研究进展及对脑血管病预防进行总结和分析,期待为脑血管病的防治提供更多帮助。 展开更多
关键词 脑血管病 神经血管影像 静脉溶栓药物 血清素 淀粉样蛋白β1-40 地中海饮食 进展
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早期生长反应因子对U87MG细胞Aβ40表达的影响
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作者 赵莘瑜 苏刚 《郑州大学学报(医学版)》 CAS 北大核心 2016年第4期513-516,共4页
目的:研究早期生长因子EGR1对U87MG细胞Aβ40表达的影响。方法:构建EGR1表达质粒并转染U87MG(实验组),以转染空白质粒的U87MG细胞作为对照。采用qRT-PCR法检测两组EGR1 mRNA的表达;收集细胞培养液用ELISA法检测Aβ40的水平;提取总蛋白... 目的:研究早期生长因子EGR1对U87MG细胞Aβ40表达的影响。方法:构建EGR1表达质粒并转染U87MG(实验组),以转染空白质粒的U87MG细胞作为对照。采用qRT-PCR法检测两组EGR1 mRNA的表达;收集细胞培养液用ELISA法检测Aβ40的水平;提取总蛋白用蛋白印迹法检测BACE1和PS1蛋白的表达。结果:质粒成功构建并表达。实验组EGR1 mRNA表达水平较对照组明显增高(P<0.001);实验组细胞培养液中Aβ40水平较对照组增高(P<0.001);实验组BACE1蛋白的表达较对照组增加(P<0.001);两组PS1蛋白的表达差异无统计学意义(P=0.367)。结论:EGR1在体外可能使Aβ40表达增加,且可能与上调BACE1有关。 展开更多
关键词 阿尔茨海默病 40 EGR1 U87MG细胞
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血清淀粉样肽1-40水平与冠心病患者冠状动脉病变的相关性及其临床意义 被引量:4
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作者 王德国 王俊 +4 位作者 孙义润 张奇 邢文 陈月云 王安才 《临床心血管病杂志》 CAS CSCD 北大核心 2016年第8期790-793,共4页
目的:探讨冠心病患者血清淀粉样肽1-40(Aβ1-40)浓度变化及其与冠状动脉(冠脉)病变的关系。方法:选取我院经造影确诊的冠心病患者300例及同期造影为非冠心病患者86例,采集基本临床资料及生化指标,以酶联免疫吸附法(ELISA法)检测Aβ1-40... 目的:探讨冠心病患者血清淀粉样肽1-40(Aβ1-40)浓度变化及其与冠状动脉(冠脉)病变的关系。方法:选取我院经造影确诊的冠心病患者300例及同期造影为非冠心病患者86例,采集基本临床资料及生化指标,以酶联免疫吸附法(ELISA法)检测Aβ1-40的浓度。Gensini评分判断冠脉病变的严重程度,分析Aβ1-40浓度与冠心病及其严重程度的相关性。结果:与对照组比较,冠心病组血清肌酐[(76.2±18.9)μmol/L∶(69.4±14.3)μmol/L,P<0.001]和Aβ1-40[(63.9±20.14)ng/L∶(55.9±17.1)ng/L,P<0.001]显著增高而高密度脂蛋白[(0.96±0.26)mmol/L∶(1.06±0.33)mmol/L,P<0.003]显著降低。Gensini评分重度(>40)的冠心病患者肌酐、葡萄糖、总胆固醇、低密度脂蛋白及Aβ1-40显著高于轻度(<20)患者(P<0.05)。相关分析显示血清Aβ1-40浓度与年龄、高血压、尿素、肌酐、高密度脂蛋白及Gensini分级等呈显著相关(P<0.05),在校正性别、年龄、高血压、肌酐、尿素及高密度脂蛋白后,Aβ1-40浓度仍与冠心病Gensini分级显著正相关(r=0.113,P=0.027)。结论:冠心病患者血清Aβ1-40显著升高,升高的Aβ1-40与冠心病冠脉Gensini分级显著正相关,提示血清Aβ1-40测定有可能成为临床冠脉病变评估的有效指标。 展开更多
关键词 血清淀粉样肽1-40 冠心病 GENSINI评分
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异氟烷全麻围术期老年患者血清淀粉样蛋白-β(1-40)与锌水平的变化 被引量:3
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作者 范隆 薛纪秀 王天龙 《药物不良反应杂志》 2009年第3期161-164,共4页
目的:观察异氟烷全麻围术期老年患者血清淀粉样蛋白-β(1-40)[Aβ(1-40)]和锌水平的变化。方法:将2007年6月至2008年3月拟开腹手术患者40例纳入研究。依年龄将患者分为2组:老年组(20例)与非老年组(20例)。老年组中男12例,女8例,平均年龄... 目的:观察异氟烷全麻围术期老年患者血清淀粉样蛋白-β(1-40)[Aβ(1-40)]和锌水平的变化。方法:将2007年6月至2008年3月拟开腹手术患者40例纳入研究。依年龄将患者分为2组:老年组(20例)与非老年组(20例)。老年组中男12例,女8例,平均年龄(72.39±4.11)岁;非老年组中男11例,女9例,平均年龄(48.15±5.62)岁。患者入手术室后行麻醉诱导和气管插管,并吸入异氟烷1~1.5最低肺泡浓度(MAC)维持麻醉。麻醉前及麻醉后2、4、24 h采集患者肘静脉血3 ml,用酶联免疫吸附试验(ELISA)和生化法分别测定血清Aβ(1-40)和锌水平。结果:老年组与非老年组患者麻醉前血清Aβ(1-40)水平分别为(5.03±1.96)μg/ml和(3.92±0.46)μg/ml,差异有统计学意义(P<0.05)。老年组与非老年组患者麻醉后2、4、24 h Aβ(1-40)水平均增高,分别为(7.95±1.66)μg/ml、(7.63±1.51)μg/ml、(6.94±1.43)μg/ml与(5.15±0.72)μg/ml、(6.34±0.99)μg/ml、(4.81±0.81)μg/ml;2组麻醉前后以及麻醉后2组间各时间点血清Aβ(1-40)水平比较差异均有统计学意义(均P<0.05)。老年组与非老年组患者麻醉前血清锌水平分别为(14.36±1.38)μg/ml和(14.64±1.75)μg/ml。老年组与非老年组患者麻醉后2、4、24 h血清锌水平分别为(12.71±1.36)μg/ml、(10.64±1.83)μg/ml、(8.07±1.61)μg/ml和(13.10±1.68)μg/ml、(11.16±1.74)μg/ml、(9.40±1.99)μg/ml;2组麻醉前后及麻醉后24 h 2组间血清锌水平比较差异均有统计学意义(均P<0.05)。结论:异氟烷全麻围手术期老年患者血清淀粉样蛋白-β(1-40)水平明显升高,血清锌降低。 展开更多
关键词 淀粉样蛋白-β(1-40) 血清锌 老年患者 异氟烷全麻 围手术期
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不同年龄糖尿病大鼠脑组织LRP-1表达与Aβ1-40的相关性 被引量:4
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作者 王苗 朱梅佳 赵张宁 《山东大学学报(医学版)》 CAS 北大核心 2010年第3期19-23,共5页
目的研究糖尿病大鼠脑组织中低密度脂蛋白受体相关蛋白1(Lrp-1)和β淀粉样蛋白(Aβ1-40)的含量,探讨二者的关系。方法采用高脂高糖饮食加小剂量腹腔注射链脲佐菌素建立2型糖尿病大鼠模型。将Wistar大鼠随机分为3月龄正常对照组、6月龄... 目的研究糖尿病大鼠脑组织中低密度脂蛋白受体相关蛋白1(Lrp-1)和β淀粉样蛋白(Aβ1-40)的含量,探讨二者的关系。方法采用高脂高糖饮食加小剂量腹腔注射链脲佐菌素建立2型糖尿病大鼠模型。将Wistar大鼠随机分为3月龄正常对照组、6月龄正常对照组、3月龄糖尿病组(DM3组)、6月龄糖尿病组(DM6组)。应用免疫组化法测定Lrp-1、Aβ1-40的表达。酶联免疫吸附试验(Elisa)法测定Lrp-1、Aβ1-40在脑组织的表达量。结果①Aβ1-40表达于大鼠大脑皮质、海马等处的神经元、神经胶质细胞的胞浆、胞膜及软脑膜动脉和穿支动脉的外膜及平滑肌细胞处;在同月龄大鼠中,糖尿病组Aβ1-40在脑组织中表达均较正常大鼠组明显增多(P<0.05);两组大鼠随着月龄的增长Aβ1-40在脑组织中的表达逐渐增加(P<0.05);②Lrp-1表达于大脑皮质、海马等处的神经元细胞的胞浆、胞膜及软脑膜动脉和穿支动脉的内膜和毛细血管内皮细胞上;在同月龄大鼠中,糖尿病组较正常大鼠组Lrp-1的表达明显减少(P<0.05);两组大鼠随月龄增长Lrp-1表达逐渐减少(P<0.05);③Aβ1-40和Lrp-1呈负相关。结论Aβ1-40沉积可能与Lrp-1的表达下调有关。 展开更多
关键词 糖尿病 脑血管 低密度脂蛋白受体相关蛋白1 Β淀粉样蛋白 大鼠 Wistar
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Analysis of hippocampal gene expression profile of Alzheimer's disease model rats using genome chip bioinformatics 被引量:1
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作者 Yinghong Li Zhengzhi Wu +5 位作者 Yu Jin Anmin Wu Meiqun Cao Kehuan Sun Xiuqin Jia Manyin Chen 《Neural Regeneration Research》 SCIE CAS CSCD 2012年第5期332-340,共9页
In this study, an Alzheimer's disease model was established in rats through stereotactic injection of condensed amyloid beta 1-40 into the bilateral hippocampus, and the changes of gene expression profile in the hipp... In this study, an Alzheimer's disease model was established in rats through stereotactic injection of condensed amyloid beta 1-40 into the bilateral hippocampus, and the changes of gene expression profile in the hippocampus of rat models and sham-operated rats were compared by genome expression profiling analysis. Results showed that the expression of 50 genes was significantly up-regulated (fold change 〉 2), while 21 genes were significantly down-regulated in the hippocampus of Alzheimer's disease model rats (fold change 〈 0.5) compared with the sham-operation group. The differentially expressed genes are involved in many functions, such as brain nerve system development, neuronal differentiation and functional regulation, cellular growth, differentiation and apoptosis, synaptogenesis and plasticity, inflammatory and immune responses, ion channels/transporters, signal transduction, cell material/energy metabolism. Our findings indicate that several genes were abnormally expressed in the metabolic and signal transduction pathways in the hippocampus of amyloid beta 1 40-induced rat model of Alzheimer's disease, thereby affecting the hippocampal and brain functions. 展开更多
关键词 amyloid beta 1-40 Alzheimer's disease HIPPOCAMPUS genome chip gene expression profile neural regeneration
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丙泊酚联合骶管阻滞对下腹部麻醉患儿的影响 被引量:10
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作者 周力 屈美敏 +3 位作者 费建 张锡凤 胡铮 陈玲玲 《中国现代医学杂志》 CAS 2018年第33期98-102,共5页
目的探究丙泊酚联合骶管阻滞对下腹部麻醉患儿血流动力学及血清人β淀粉样蛋白1-42(Aβ_(1-42))、人β淀粉样蛋白1-40(Aβ_(1-40))的影响。方法选取2016年2月-2017年4月在儿童医院行下腹部手术的患儿73例作为研究对象,根据随机数字表法... 目的探究丙泊酚联合骶管阻滞对下腹部麻醉患儿血流动力学及血清人β淀粉样蛋白1-42(Aβ_(1-42))、人β淀粉样蛋白1-40(Aβ_(1-40))的影响。方法选取2016年2月-2017年4月在儿童医院行下腹部手术的患儿73例作为研究对象,根据随机数字表法分为对照组(36例)和观察组(37例)。对照组患儿采用氯胺酮﹑丙泊酚复合静脉麻醉的麻醉方式,观察组患儿采用丙泊酚联合骶管阻滞的麻醉方式。比较两组患儿的麻醉效果﹑血流动力学指标﹑血清Aβ_(1-42)和Aβ_(1-40)水平及不良反应的发生情况。结果观察组患儿的麻醉诱导时间、苏醒时间均短于对照组(P<0.05);观察组与对照组收缩压、舒张压及心率组内、组间及时间变化趋势有差异(P<0.05),观察组变化趋势较小;麻醉前后两组患儿Aβ_(1-40)和Aβ_(1-42)水平的比较,差异均无统计学意义(均P>0.05);观察组患儿各种不良反应的发生率均低于对照组(P<0.05)。结论丙泊酚联合骶管阻滞对行下腹部手术的患儿进行麻醉时,麻醉效果好,对血流动力学及血清Aβ_(1-42)、Aβ_(1-40)的影响小,因而发挥作用更为平稳、且不良反应的发生率低,值得推广应用。 展开更多
关键词 丙泊酚 骶管阻滞 麻醉 人β淀粉样蛋白1-42(Aβ1-42) 人β淀粉样蛋白1-40(Aβ1-40)
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Can blood amyloid levels be used as a biomarker for Alzheimer's disease?
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作者 Yuan-Han Yang Rocksy FV Situmeang Paulus Anam Ong 《Brain Science Advances》 2021年第1期17-25,共9页
Alzheimer’s disease(AD)increasingly affects society due to aging populations.Even at pre-clinical stages,earlier and accurate diagnoses are essential for optimal AD management and improved clinical outcomes.Biomarker... Alzheimer’s disease(AD)increasingly affects society due to aging populations.Even at pre-clinical stages,earlier and accurate diagnoses are essential for optimal AD management and improved clinical outcomes.Biomarkers such as beta-amyloid(Aβ)or tau protein in cerebrospinal fluid(CSF)have been used as reliable markers to distinguish AD from non-AD,and predicting clinical outcomes,to attain these goals.However,given CSF access methods’invasiveness,these biomarkers are not used extensively in clinical settings.Blood Aβhas been proposed as an alternative biomarker since it is less invasive than CSF;however,sampling heterogeneity has limited its clinical applicability.In this review,we investigated blood Aβas a biomarker in AD and explored how Aβcan be facilitated as a viable biomarker for successful AD management. 展开更多
关键词 Alzheimer’s disease amyloid precursor protein 1-40 1-42 apolipoprotein E cerebrospinal fluid plasma
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