知母皂苷元及其异构体对老年大鼠学习记忆和脑内M_1受体密度的影响

目的　观察知母皂苷元 (ZMS)及其异构体 (ZMR)对老年大鼠学习记忆和脑内M1受体密度的作用。方法　选择 2 4mon龄SD老年大鼠 ,将动物分为老年对照组、ZMS组和ZMR组 ,并以 3～ 4mon龄青年大鼠作为正常对照 ,用迷宫法测定学习记忆能力 ,采用放射配基结合分析法测定脑内M1受体密度。结果　用药组大鼠连续口服ZMS和ZMR 4 0d后 ,与老年对照组比较 ,其学习记忆能力明显增强 ,脑内M1受体密度升高。结论　知母皂苷元及其异构体对老年性痴呆的胆碱能系统功能渐进性退化有一定的预防和治疗作用     

知母皂苷元对拟痴呆大鼠β-淀粉样肽沉积及胆碱能系统功能的影响

目的　观察知母皂苷元 (ZMS)对拟痴呆大鼠模型脑内 β 淀粉样肽沉积及胆碱能系统功能的作用。 方法　单侧基底核内联合注射 β 淀粉样肽2 5-3 5片段 (β AP2 5-3 5)和兴奋性氨基酸建立大鼠拟痴呆模型 ,然后将模型动物分为假手术组 37、模型组和ZMS组 ,采用免疫组织化学方法和图像分析法测定β AP2 5-3 5沉积斑块的面积。用避暗法及跳台法测定动物的学习记忆功能 ,用放射配基结合分析法分别测定脑胆碱乙酰转移酶 (ChAT)活性和M受体密度。结果　一次性脑内联合注射 β AP +IBO后 ,模型大鼠脑内有明显的 β AP斑块沉积 ,而模型大鼠喂服ZMS 6 0d后 ,能有效地减少β AP沉积的面积 ,同时ZMS能明显改善模型动物的学习记忆功能 ,并提高模型动物脑内ChAT活性和M受体密度。结论　ZMS可能对脑内 β AP的沉积有一定的清除作用 ,并对AD低下的胆碱能系统功能有一定的改善和治疗作用     

知母皂苷元对拟痴呆大鼠β-淀粉样肽沉积及胆碱能系统功能的影响

目的　观察知母皂苷元 (ZMS)对拟痴呆大鼠模型脑内 β 淀粉样肽沉积及胆碱能系统功能的作用。 方法　单侧基底核内联合注射 β 淀粉样肽2 5-3 5片段 (β AP2 5-3 5)和兴奋性氨基酸建立大鼠拟痴呆模型 ,然后将模型动物分为假手术组 37、模型组和ZMS组 ,采用免疫组织化学方法和图像分析法测定β AP2 5-3 5沉积斑块的面积。用避暗法及跳台法测定动物的学习记忆功能 ,用放射配基结合分析法分别测定脑胆碱乙酰转移酶 (ChAT)活性和M受体密度。结果　一次性脑内联合注射 β AP +IBO后 ,模型大鼠脑内有明显的 β AP斑块沉积 ,而模型大鼠喂服ZMS 6 0d后 ,能有效地减少β AP沉积的面积 ,同时ZMS能明显改善模型动物的学习记忆功能 ,并提高模型动物脑内ChAT活性和M受体密度。结论　ZMS可能对脑内 β AP的沉积有一定的清除作用 ,并对AD低下的胆碱能系统功能有一定的改善和治疗作用     

涤痰汤对老年轻度认知功能障碍大鼠海马NGFβ、BDNF含量的影响

目的:观察涤痰汤对老年轻度认知功能障碍大鼠学习记忆能力及海马组织神经生长因子(NGFβ)、脑源性神经营养因子(BDNF)含量的影响。方法:采用中年大鼠颈部皮下注射D-半乳糖结合半高脂饮食建立老年轻度认知功能障碍大鼠模型。将60只大鼠随机分为正常组、模型组、西药组、涤痰汤高剂量组(以下简称"涤高组")、涤痰汤低剂量组(简称"涤低组"),另设12只3月龄青年大鼠作为青年对照组。采用Morris水迷宫检测大鼠学习记忆能力,免疫比色法检测大鼠血清、大脑皮质超氧化物歧化酶(SOD)、丙二醛(MDA)水平;通过酶联免疫吸附法(ELISA)检测大鼠NGFβ、BDNF的含量。结果:与模型组相比,涤高组、涤低组潜伏期均明显缩短(P<0.05),血清、皮质SOD水平显著升高(P<0.05),MDA水平均显著下降(P<0.05)。涤高组海马NGFβ、BDNF含量均增加(P<0.05),涤低组海马组织BDNF含量明显升高(P<0.05)。结论:涤痰汤可能通过增加大鼠海马NGF、BDNF蛋白表达,改善老年认知功能障碍大鼠的学习记忆能力。     

脐血单核细胞对VD大鼠认知功能及脑组织BDNF的影响

目的观察颈内动脉输注脐血单核细胞(Human cord blood mononuclear cells,HCMNCs)对血管性痴呆(Vascular dementia,VD)大鼠认知功能及脑组织脑源性神经营养因子(Brain-derivedneurotrophicfactor,BDNF)含量的影响。方法改良Pulsinellis四血管阻断法建立VD大鼠模型;体外分离HCMNCs,术后24h颈内动脉输注数量为3×106/0.5ml的BrdU标记细胞;利用穿梭箱系统和ELISA法检测注射HCMNCs后2、4、8周VD大鼠学习记忆能力以及脑组织BDNF含量的变化。结果模型组大鼠主动回避反应比率明显低于对照组(P<0.01),治疗组较模型组显著提高(P<0.01)。术后2周模型组大鼠脑组织BDNF含量较对照组明显增高(P<0.01),4周时达到高峰(P<0.01),8周时则明显下降,与2周时相比有显著性差异(P<0.05);颈内动脉输注HCMNCs后治疗组大鼠脑组织BDNF含量较模型组显著升高(P<0.01),4周时最高(P<0.01),8周时略有下降,但仍维持在较高水平,与4周时相比无显著性差异(P>0.05)。结论颈内动脉输注HCMNCs可显著改善VD大鼠学习记忆能力,增加VD大鼠脑组织BDNF含量,具有脑保护作用。     

知母皂苷元对拟痴呆大鼠β-淀粉样肽沉积及胆碱能系统功能的影响

目的观察知母皂苷元(ZMS)对拟痴呆大鼠模型脑内β-淀粉样肽沉积及胆碱能系统功能的作用.方法单侧基底核内联合注射β-淀粉样肽25-35片段(β-AP25-35)和兴奋性氨基酸建立大鼠拟痴呆模型,然后将模型动物分为假手术组37、模型组和ZMS组,采用免疫组织化学方法和图像分析法测定β-AP25-35 沉积斑块的面积.用避暗法及跳台法测定动物的学习记忆功能,用放射配基结合分析法分别测定脑胆碱乙酰转移酶(ChAT)活性和M受体密度.结果一次性脑内联合注射β-AP+IBO后,模型大鼠脑内有明显的β-AP斑块沉积,而模型大鼠喂服ZMS 60 d后,能有效地减少β-AP沉积的面积,同时ZMS能明显改善模型动物的学习记忆功能,并提高模型动物脑内ChAT活性和 M受体密度.结论 ZMS可能对脑内β-AP的沉积有一定的清除作用,并对AD低下的胆碱能系统功能有一定的改善和治疗作用.     

半夏泻心汤对高龄合并D-半乳糖诱导衰老模型大鼠的影响

目的:研究半夏泻心汤对衰老模型大鼠学习记忆能力和脑内神经递质的影响。方法:高龄大鼠ip D-半乳糖125 mg.kg~(-1),每天1次,连续4周造成衰老模型动物,用水迷宫检测衰老大鼠学习记忆能力,用Elisa法检测脑组内多巴胺(DA)、去甲肾上腺素(NE)和五羟色胺(5-HT)等的含量,用Elisa法检测血清降钙素相关基因肽(CGRP)、内皮素-1(ET-1)的水平,用免疫组织化学方法检测脑组织内脑源性神经营养因子(BDNF)的表达。结果:半夏泻心汤给药组可明显缩短逃避潜伏期;半夏泻心汤10和5 g.kg~(-1)给药组海马区脑组织内DA和5-HT含量明显升高,可明显上调脑组织额叶皮层区BDNF的表达,但半夏泻心汤对血清CGRP和ET-1未见明显影响。结论:半夏泻心汤对衰老模型大鼠脑内单胺类神经递质水平与额叶皮层BDNF的表达有显著影响。     

脑益康对阿尔茨海默病模型小鼠学习记忆的影响

目的 :观察脑益康对阿尔茨海默病 (Alzhei mer’sdisease ,AD)模型小鼠学习记忆的影响 ,并探讨其改善学习记忆的机制。方法 :采用D 半乳糖 (D Gal)和亚硝酸钠 (NaNO2 )腹腔注射建立小鼠AD模型 ,通过迷宫刺激器和水迷宫实验检测小鼠学习记忆能力 ;生化方法检测小鼠脑组织内超氧化物歧化酶 (SOD)活性和丙二醛 (MDA)含量 ;透射电镜观察小鼠海马神经细胞的超微结构。结果 :模型对照组小鼠学习记忆能力下降 ,SOD活性降低 ,MDA含量升高 ;而与模型对照组比较 ,脑益康小、中、大剂量组(2 .4、7.2、2 4g·kg-1·d-1)均可显著改善模型小鼠的学习记忆能力 ,提高脑内SOD活性 ,降低脑内MDA含量 (P <0 .0 1或P <0 .0 5 ) ,阻抑海马神经细胞的退行性变化。结论 :脑益康可改善D 半乳糖和亚硝酸钠所致AD模型小鼠的学习记忆能力。     

大黄酚对铅中毒小鼠学习记忆的改善作用及其机制研究

目的研究大黄酚对铅中毒小鼠学习记忆障碍的改善作用,探讨其可能的作用机制。方法采用连续8 d腹腔注射7 mg.kg-1醋酸铅造成铅中毒小鼠模型,应用避暗实验、水迷宫实验,观察腹腔注射大黄酚(10.0、1.0、0.1 mg.kg-1)14 d对铅中毒模型小鼠记忆障碍的改善作用,大黄酚治疗14 d后测定小鼠血铅、脑铅及脑组织中MDA含量SOD,GSH-Px活力,一氧化氮(NO)含量及一氧化氮合酶(NOS)、诱导型一氧化氮合酶(iNOS)的活性。结果连续8 d腹腔注射7 mg.kg-1醋酸铅造成铅中毒小鼠学习记忆障碍,使小鼠脑铅、血铅升高,导致小鼠脑组织内SOD和GSH-Px活性降低,使小鼠脑组织内MDA含量增加,小鼠脑组织内NO含量增加,NOS和iNOS活性升高;连续ip大黄酚14d治疗后,可不同程度改善小鼠铅中毒造成的学习记忆障碍,降低血铅及脑铅水平,大黄酚(0.1 mg.kg-1)可升高铅中毒小鼠脑内SOD和GSH-Px的活性(P<0.01),对MDA含量无影响;大黄酚(10.0、1.0 mg.kg-1)可升高铅中毒小鼠脑内SOD和GSH-Px的活性,降低小鼠脑内MDA含量(P<0.01);大黄酚(0.1 mg.kg-1)可降低小鼠脑内NOS、iNOS的活性(P<0.05),对NO含量无影响;大黄酚10.0,1.0 mg.kg-1治疗组可降低小鼠脑内NO含量和NOS、iNOS的活性(P<0.01)。结论大黄酚通过提高铅中毒小鼠脑组织抗氧化酶活性同时降低NOS、iNOS的活性,抑制脂质过氧化,明显拮抗铅诱导的小鼠学习记忆障碍。     

益智膏滋对血管性痴呆大鼠脑损伤的作用研究

摘 要 目的：观察益智膏滋对血管性痴呆大鼠模型的影响。方法: 采用结扎双侧颈总动脉法制备血管性痴呆大鼠模型。益智膏滋高、中、低各剂量组大鼠连续灌胃给药30 d,采用Morris水迷宫的方法观察益智膏滋对大鼠学习记忆障碍的改善作用;采用生化方法检测各组大鼠血清中乙酰胆碱（Ach）、一氧化氮（NO）含量及一氧化氮合酶（NOS）活力;计算脑指数观察脑水肿状态;HE染色观测各组大鼠脑组织病理结构变化。结果: 与模型组相比,益智膏滋各给药组大鼠逃避潜伏期明显缩短(P<0.05),3min内找到平台次数明显增多(P<0.05),Ach含量明显升高(P<0.05),NO含量和NOS活力明显降低(P<0.05),脑指数明显降低(P<0.05),脑组织病理形态显著改善。结论: 益智膏滋能够明显提高血管性痴呆大鼠学习记忆能力,改善大鼠的脑水肿状态及脑组织病理形态,其作用机制与降低血清中NO含量和NOS活力,增强大鼠机体抗氧化损伤的能力,减轻脑组织损伤,进而提高Ach含量,增强胆碱能神经功能有关。     

山茱萸多糖对青霉素致痫幼鼠学习记忆能力及海马组织脑源性神经因子、神经生长因子表达的影响

目的:探讨山茱萸多糖对青霉素致痫幼鼠学习记忆能力及海马组织脑源性神经因子(BDNF)、神经生长因子(NGF)表达的影响。方法:将30只日龄21 d龄幼鼠随机分为生理盐水对照组、青霉素点燃模型组、山茱萸多糖处理组各10只。生理盐水对照组只接受生理盐水灌胃,不造模;山茱萸多糖处理组在造模成功后灌胃0.05 g/mL山茱萸多糖;青霉素点燃模型组造模成功后灌胃等量生理盐水;连续灌胃28 d。采用Morris水迷宫检测各组幼鼠学习记忆能力;RT-PCR法检测海马组织BDNF mRNA、NGF mRNA表达;Western-blot法检测海马组织BDNF与NGF蛋白含量。结果:与生理盐水对照组比较,青霉素点燃模型组幼鼠学习记忆能力明显降低(P<0.01);与模型组比较,山茱萸多糖处理组学习记忆能力明显升高(P<0.01)。与生理盐水对照组比较,青霉素点燃模型组幼鼠BDNF、NGF mRNA和蛋白表达明显降低(P<0.01);与模型组比较,山茱萸多糖处理组BDNF、NGF mRNA和蛋白表达明显升高(P<0.01)。结论:山茱萸多糖具有提高青霉素点燃幼鼠学习记忆能力的作用,其机制可能是通过上调BDNF和NGF基因表达。     

The influence of orally administered docosahexaenoic acid on monoamine neurotransmitter,nerve growth factor,and brain-derived neurotrophic factor in aged mice

In this study we attempt to investigate the new role of docosahexaenoic acid (DHA) supplementation on cognitive ability in aged mice. Kunming-line mice were treated with DHA (200, 400?mg/kg body weight/day) for 30 successive days. The cognitive ability of mice was assessed by learning and memory behavioral test; the levels of DHA were assessed by capillary gas chromatography; the levels of dopamine (DA), norepinephrine (NE), and 5-hydroxytryptamine (5-HT) were assessed by high-performance liquid chromatography; the levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) proteins were assessed by the enzyme-linked immunosorbent assay method. The results showed the cognitive ability of mice were significantly different between the DHA-treated groups and the aged group, and orally administered DHA can increase the levels of DA, NE and 5-HT, the content of BDNF and NGF proteins in hippocampus, frontal cortex and striatum tissues. In addition, aged-related changes in phospholipid DHA content were seen. Decreases in DHA were mostly corrected by DHA supplementation. These novel data suggest that DHA supplementation can improve the cognitive dysfunction due to aging by increasing the levels of BDNF and NGF protein and the levels of DA, NE, 5-HT to some extent. We speculate that the mechanism of DHA on cognitive ability may have a beneficial effect on signaling networks through modulation of monoamine neurotransmitters and neurotrophic factors in brain aging.     

ZDY102对拟痴呆大鼠脑M受体的影响

目的　观察知母活性成分ZMS的异构体ZDY10 2对拟痴呆大鼠脑M受体及学习记忆功能的影响。方法　大鼠单侧脑基底核部位定位注射 β 淀粉样肽 (2 5～ 35 )和鹅蕈膏酸造成拟痴呆模型 ,设立不同剂量ZDY10 2治疗组、模型组和对照组 (注射生理盐水 ) ,分别用Y 迷宫测定学习记忆能力及放射配基结合分析法测定注射同侧脑内M胆碱受体密度。结果　拟痴呆模型大鼠学习和记忆成绩和脑M受体密度明显低于对照组。连续两个月喂服ZDY10 2的模型大鼠学习和记忆能力显著好于对照组 ,脑M受体密度也显著提高 ,而且脑M受体密度与动物的学习记忆能力呈显著正相关。结论　ZDY10 2能明显改善拟痴呆大鼠的学习记忆能力 ,同时能显著提高脑内M受体密度 ,从两者的显著正相关来看 ,提高脑M受体密度可能是ZDY10 2改善拟痴呆模型学习记忆的重要机制。和以往对知母活性成分的研究结果相比较可以看出 ,2 5位甲基的立体异构对上述效果无明显影响     

Prenatal methylazoxymethanol acetate alters behavior and brain NGF levels in young rats: a possible correlation with the development of schizophrenia-like deficits.

It has been hypothesized that a deleterious key contribution to schizophrenia (SZ) development is a failure of migration and setting of young neurons into their appropriate cortical target sites, particularly in the entorhinal cortex (EC). To test this hypothesis in an animal model, we injected, in pregnant rats, on gestational day (GD) 9, or 10, or 11, or 12, the antimitotic compound methylazoxymethanolacetate (MAM) known to cause EC neuronal loss. We investigated whether or not EC disruption during prenatal development is able to affect behavior, including memory and learning, and brain nerve growth factor (NGF). Prenatally MAM treated young rats didn't display gross behavioral changes in social interaction, open-field and novel object investigation tests. By contrast, GD11 and GD12 MAM treated rats had a retardation in passive avoidance acquisition, while, in GD12 animals, pain sensitivity was reduced. GD12 animals also showed increased NGF in the EC and remaining cortex. MAM treated animals showed no changes in paw NGF or substance P levels suggesting that the altered nociceptive response is not related to local downregulation of these two molecules. The possibility that these behavioral and biochemical alterations might be associated with the onset of SZ is discussed.     

Long-lasting effects of prenatal MAM treatment on water maze performance in rats: associations with altered brain development and neurotrophin levels

We previously reported that prenatal methylazoxymethanol (MAM) administered on days 11 and 12 of rat pregnancy induces structural changes in the cytoarchitecture of the hippocampal-entorhinal axis. We also showed that young and middle-aged prenatally treated MAM animals displayed changes in brain neurotrophin levels [Neurosci. Lett. 309 (2001) 113; Physiol. Behav. 71 (2000) 57.]. To continue this line of investigation, the working hypothesis adopted was that prenatal MAM administration, by interfering with limbic neurogenesis, could impair learning and memory ability of aged animals in the water maze. It was found that injection of MAM during early rat brain development induced deficits in both the acquisition and retention phases of the Morris maze. These behavioral changes were associated with significant changes in brain nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), reduced choline acetyltransferase (ChAT) immunoreactivity in forebrain cholinergic neurons and loss of neuropeptide Y (NPY) immunodistribution in cells of the entorhinal cortex. This finding, as well as confirming previous studies showing that injection of prenatal MAM administration induces significant changes in hippocampal-entorhinal axis neurogenesis and marked behavioral deficits in adult life, provides additional experimental evidence supporting the hypothesis that loss of NGF and/or BDNF-receptive or producing cells can co-occur at the onset of neurodevelopmental disorders.     

What is the combined effect of intense intermittent exercise and Ginkgo biloba plant on the brain neurotrophic factors levels,and learning and memory in young rats?

BackgroundThe present study was conducted to investigate the effect of intense intermittent exercise and Ginkgo biloba on the hippocampal levels of brain‐derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) and also memory and learning in young rats.MethodsForty two eight-week-old rats were randomly divided into six groups including control, low dose of Ginkgo biloba (65 mg/kg), high dose of Ginkgo biloba (100 mg/kg), exercise, exercise + low dose of Ginkgo biloba, exercise + high dose of Ginkgo biloba. The exercise protocol or Ginkgo biloba administration was six days a week for six weeks. The hippocampal levels of BDNF and NT-4 were measured by ELISA method, and learning and memory were evaluated by Morris water maze test in all groups. Data were analyzed using SPSS software.ResultsIncrease in hippocampal levels of BDNF and NT-4 appeared following exercise (p < 0.01). The levels do not change following exercise + Ginkgo biloba administration. However, the NT-4 level decreased in the high dose of Ginkgo biloba group (p < 0.01). Disorder in learning and memory was indicated following the use of low dose of Ginkgo biloba or exercise + low dose Ginkgo biloba administration (p < 0.001). Learning elevated in the exercise group (p < 0.05).ConclusionsExercise in young rats may increase brain neurotrophin levels and lead to improved learning. The preventative or protective role of Ginkgo biloba against some diseases has been suggested, but its consumption in young athletes is recommended with caution.     

出生前后铝暴露对大鼠学习记忆及海马NO、nNOS的影响

目的研究出生前后不同浓度慢性铝暴露后年轻大鼠海马NO含量和nNOS表达的变化,探讨铝损害学习记忆的突触机制。方法对照组、低剂量和高剂量组大鼠从孕期开始分别自由饮用蒸馏水15mmol.L-1和30mmol.L-1的A1C13水溶液;采用原子吸收石墨炉法测定血铝和脑铝含量;跳台法测试学习记忆能力;硝酸还原酶法检测NO含量;免疫组化方法观察nNOS阳性细胞表达。结果与对照组相比,两铝暴露组大鼠血铝和脑铝含量明显升高,学习记忆能力明显下降,海马NO含量明显降低且nNOS阳性神经元表达明显减少。结论出生前后慢性铝暴露损害了大鼠的学习记忆行为,可能与海马NO含量减少及nNOS神经元表达降低有关。