蛇床子素减轻脂多糖诱导的大鼠学习记忆减退

目的观察蛇床子素对脂多糖诱导的大鼠学习记忆减退的作用,并初探其可能的作用机制。方法 40只雄性SD大鼠随机分为假手术组、模型组、阳性药组及蛇床子素组。阳性药组、蛇床子素组分别每日1次灌胃布洛芬、蛇床子素40 mg.kg-1,连续12 d,假手术组、模型组灌胃等体积的生理盐水,3 d后侧脑室注射脂多糖诱导大鼠的神经炎症模型,制模后d 5开始Morris水迷宫检测大鼠的空间记忆能力,连续5 d。Morris水迷宫检测结束后,处死大鼠,HE染色观察大鼠海马神经元损伤情况,real time RT-PCR法测定海马肿瘤坏死因子α(Tnf-α)、白细胞介素-1β(Il-1β)、诱导型一氧化氮合酶(Nos2)及环氧合酶-2(Cox-2)的mRNA表达。结果侧脑室注射脂多糖后,大鼠在定向航行实验中的逃避潜伏期显著增加(P<0.05),空间探索实验中的校正逃避潜伏期缩短(P<0.05),海马神经元明显受损,且海马Tnf-α、Il-1β、Nos2及Cox-2的mRNA表达增加(P<0.05);然而,蛇床子素及布洛芬明显缩短了大鼠的定向航行实验中的逃避潜伏期(P<0.05),延长了空间探索实验中的校正逃避潜伏期(P<0.05),减轻了海马神经元损伤,且降低海马Tnf-α、Il-1β、Nos2及Cox-2的mRNA表达。结论蛇床子素可减轻脂多糖诱导的大鼠学习记忆减退及海马神经元损伤,其机制与抑制炎症相关基因的mRNA表达有关。     

白藜芦醇对大鼠慢性肝纤维化的影响

目的:观察白藜芦醇对四氯化碳(CCl4)致大鼠慢性肝纤维化的影响.方法:Wistar大鼠皮下注射50?l4 1 mL·kg-1,每周2次,共10周.设白藜芦醇25,50,100 mg·kg-1组,每组10只大鼠,连续灌服6周.检测大鼠血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总蛋白(TP)和白蛋白(ALB)水平,测量肝组织羟脯氨酸(Hyp)和丙二醛(MDA)水平,肝组织胶原纤维染色后半定量分析和肝组织病理组织学检查.结果:高剂量组的ALT明显低于模型对照组(P<0.01).中剂量组和高剂量组肝组织Hyp和MDA水平、胶原化程度明显低于模型对照组.结论:白藜芦醇对肝纤维化可能有治疗作用.     

金钗石斛生物总碱对脂多糖诱导的大鼠学习记忆减退的保护作用及机制

目的：观察增龄大鼠海马神经生长因子（NGF）及其受体后磷脂酰肌醇-3激酶（PI3K）信号转导通路的变化，并应用参乌胶囊（SW）及二苯乙烯苷（TSG）对老年大鼠进行干预，为揭示药物防治老年性痴呆的作用机理提供多方面的实验依据。方法：雄性SD大鼠，按月龄分为1、3、6、18和24月龄。24月龄老年大鼠分为对照组、SW组、TSG组。从21月龄开始，分别给予SW和TSG灌胃，至24月龄．应用免疫组织化学染色方法观察海马CA1区神经元NGF及其受体TrkA、胰岛素受体底物-1（IRS-1）、PI3K、丝氨酸／苏氨酸蛋白激酶B（Akt／PKB）、磷酸化的70KDa S6核糖体蛋白激酶（P-p70S6K）表达情况。应用Western blot方法对上述部分因子进行半定量分析，并进一步检测了磷酸化的cAMP反应元件结合蛋白（p—CREB）。结果：神经元存活信号转导通路相关因子的蛋白质表达呈现随增龄变化趋势，表现为幼年期表达水平较低，逐渐升高至青中年期表达达高峰，进入老年期表达下降；但其中不同因子的表达各具特点，通路起始部位的因子NGF、TrkA、IRS-1和通路末端的因子p—p70S6K、p—CREB随增龄变化明显，而中间的因子Akt变化不大。SW和TSG可以上调老年大鼠海马神经元NGF、TrkA、IRS-1、PI3K、p—p70S6K、p—CREB的表达水平。结论：参乌胶囊和二苯乙烯苷具有上调老年大鼠海马神经元NGF及TrkA受体、激活老年大鼠海马神经元PI3K信号转导通路的作用。     

加巴喷丁减轻骨折模型大鼠焦虑情绪及海马神经炎症的作用机制研究

目的 探析加巴喷丁对骨折模型大鼠焦虑情绪、海马神经炎症、人核因子κB(NF-κB)/肿瘤坏死因子α(TNF-α)信号通路的影响。方法 自2022年1―6月,选择健康雄性无特定病原体（SPF）SD大鼠48只,采用随机数字表法分为假手术组、模型组、治疗组。假手术组正常饲养,未做任何处理,其余两组大鼠均进行骨折造模。其中治疗组给予加巴喷丁治疗,模型组给予等量生理盐水干预,连续给药12 d。采用高架十字迷宫实验评估大鼠焦虑情绪;采用酶联免疫吸附（ELISA）检测白细胞介素-4(IL-4)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、超氧化物歧化酶（SOD）、丙二醛（MDA）,采用比色法检测谷胱甘肽过氧化物酶（GSH-Px）。采用苏木素伊红（HE）染色评估海马组织病理形态特征;采用蛋白质印迹法检测TNF-α、NF-κB蛋白表达量。结果 假手术组、治疗组、模型组总穿臂次数（TE）、进入比例（OE）、停留时间比例（OT）比较,假手术组大鼠TE[(12.31±2.59)次比（10.29±2.37）次、（7.25±2.16）次]、OE[(40.25±5.41)%比（37.02±5.13）...     

老年学习记忆减退机制的研究进展

随着机体的老化学习记忆出现了明显减退 ,其机制复杂多样 ,可能与老年时学习记忆相关脑区突触形态与功能 ,中枢神经递质系统以及脑内钙离子浓度、基因表达、神经营养等发生改变有关。该文简要综述近年老年学习记忆减退机制的研究进展。     

白藜芦醇联合厄贝沙坦对博莱霉素所致大鼠肺纤维化肺组织的保护作用及机制研究

目的 探讨白藜芦醇联合厄贝沙坦对博莱霉素所致大鼠肺纤维化肺组织的保护作用及作用机制.方法 108只雄性大鼠,按随机数字表法分为A、B和C组,每组36例.3组均予博莱霉素制备肺纤维化模型,模型建立成功后A组予生理盐水灌胃,B组予厄贝沙坦灌胃,C组在B组基础上给予白藜芦醇灌胃,治疗7d后比较3组血清转化生长因子(TGF-β1)、解聚蛋白样金属蛋白酶(ADAMTS-1)、Ⅰ型胶原(Col Ⅰ)、Ⅲ型胶原(Col Ⅲ)及血清Ⅰ型前胶原羧基端肽(PI CP)和Ⅲ型前胶原氨基端前肽(PⅢNP)、血清肿瘤坏死因子-α(TNF-α)、白介素(IL)-6、IL-17的表达水平、肺组织羟脯氨酸(HYP)、丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)及过氧化氢酶(CAT)含量.结果 B、C组ADAMTS-1、Col Ⅰ、ColⅢ、HYP、SOD、GSH-Px及CAT均较A组升高,TGF-β1、PⅠCP和PⅢNP、TNF-α、IL-6、IL-17、MDA较A组降低,C组ADAMTS-1、Col Ⅰ、ColⅢ、HYP、SOD、GSH-Px及CAT高于B组,TGF-β1、PⅠ CP和PⅢNP、TNF-α、IL-6、IL-17、MDA水平低于B组(P＜0.05).B、C组肺泡炎症及肺纤维化程度轻于A组,且C组轻于B组(P＜0.05).结论 白藜芦醇联合厄贝沙坦对肺纤维化大鼠的肺组织具有一定的保护作用,其可能通过降低TGF-β1水平使ADAMTS-1含量升高,降低Col Ⅰ和ColⅢ水平从而起到抗纤维化的作用.     

间断注射小剂量脂多糖建立大鼠的慢性炎症模型

目的探讨小剂量脂多糖(LPS)间断注射建立大鼠慢性炎症模型的可行性。方法将40只SD大鼠随机均分为对照组与LPS处理1、2、3、4周组。除对照组外的各组大鼠尾静脉注射LPS(0.2 mg·kg-1·w-1),对照组注射等体积生理盐水。观察各组大鼠存活情况,检测血白细胞计数与分类、血清白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、超敏C反应蛋白(hs-CRP),以及心、肝、肺、肾HE染色镜检。结果大鼠全部存活。尾静脉注射LPS后大鼠血白细胞总数、中性粒细胞比例及血清IL-6、TNF-α、hs-CRP水平均增高,淋巴细胞比例降低,心、肝、肺、肾出现以炎性细胞浸润、组织淤血水肿为主的病理变化。结论 SD大鼠小剂量间断尾静脉注射LPS可诱导典型慢性炎症,可供LPS相关慢性炎症的长期研究之用。     

七氟醚对老龄大鼠空间学习和记忆能力的影响

目的通过Morris水迷宫实验,探讨七氟醚对老龄大鼠空间学习和记忆能力的影响。方法选取18月龄,450~500 g,健康雄性SD大鼠24只,随机分为4组。大鼠于麻醉前进行Morris水迷宫适应性训练3 d,于麻醉结束后1、3、7 d进行M orris水迷宫实验测定空间学习和记忆能力。结果 1定位航行实验。组间比较:麻醉后1、3 d,I组、S1组逃避潜伏期较C组延长(P<0.05);麻醉后3 d,I组、S1组总游泳距离较C组延长(P<0.05);麻醉后7 d,I组逃避潜伏期和总游泳距离较C组、S1组延长(P<0.05)。组内比较:与麻醉后1 d比较,麻醉后3、7 d各组逃避潜伏期和总游泳距离均延长(P<0.05,P<0.01)。2空间探索实验。S1组、S2组的平台象限的停留时间(TP)和TP与总游泳时间的百分比(TP/T)与C组比较差异均有统计学意义(P<0.05),I组与C组比较差异有统计学意义(P<0.01)。结论低浓度七氟醚对老龄大鼠早期空间学习和记忆能力无明显影响。高浓度七氟醚、异氟醚均可引起老龄大鼠早期空间学习和记忆能力一过性下降,但这些变化均在麻醉后第7天趋于恢复,且七氟醚恢复较异氟醚快。     

FLZ attenuates learning and memory deficits via suppressing neuroinflammation induced by LPS in mice

Alzheimer's disease (AD) is the most common neurodegenerative disorder in which neuroinflammation plays an important role. FLZ is a novel synthetic derivative of natural squamosamide. Previous studies demonstrated that FLZ had neuroprotective effects on AD models and showed strong anti-inflammatory property in Parkinson's disease models. However, whether the neuroprotective effects of FLZ on AD are associated with its anti-inflammatory property is still not fully elucidated. In this study, we aimed to investigate the ability of FLZ in modulating inflammation. The results showed that FLZ significantly improved memory deficits and alleviated neuronal damage as well as neuronal loss in the hippocampus of mice intracerebroventricular injected with lipopolysaccharide (LPS). Mechanistic studies revealed that the neuroprotective effects of FLZ were due to the suppression of neuroinflammation induced by LPS, as indicated by inactivation of astrocytes and microglia, reduced production of tumor necrosis factor-α, interleukin-1β, and nitric oxide, as well as decreased expression of cyclooxygenase-2 and inducible nitric oxide synthase. The beneficial effects of FLZ on AD were further supported by the finding that FLZ attenuated β-amyloid production through inhibiting β-amyloid precursor protein cleaving enzyme 1 expression. These results suggested that anti-inflammatory agent could be useful for the treatment of AD.     

Protective effects of icariin against learning and memory deficits induced by aluminium in rats

1. The present study examined the protective effects of icariin against the learning and memory deficits in aluminium-treated rats and its potential mechanisms of action. 2. Qualified rats were treated with 1600 p.p.m. AlCl(3) in drinking water for 8 months and the ability of spatial learning and memory was tested by the Morris water maze. In the place navigation test, aluminium administration significantly increased the mean escape latency and searching distance. In space probing test, aluminium markedly decreased the searching time and searching distance in the quadrant where the platform was originally located. All tests indicated deficits in rat spatial learning and memory induced by aluminium. Icariin treatment (60 and 120 mg/kg, by gavage for 3 months) dose-dependently protected against the development of aluminium-induced spatial learning and memory deficits. 3. To examine the mechanisms responsible for the protection afforded by icariin, the superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in the hippocampus were assayed biochemically and the level of Abeta(1-40) in the hippocampus was determined immunohistochemically. Icariin treatment significantly increased SOD activity and decreased MDA and Abeta(1-40) content in the hippocampus of aluminium-intoxicated rats. 4. In conclusion, the present study demonstrates that icariin is effective in improving the spatial learning and memory of aluminium-intoxicated rats. The mechanisms responsible appear to be due, at least in part, to an increased anti-oxidant capacity and decreased lipid peroxidation and Abeta(1-40) levels in the rat hippocampus.     

TAK—147逆转东莨菪碱诱发的大鼠空间记忆障碍

目的:研究和阐明TAK-147对东莨菪碱诱发的大鼠空间记忆损伤的作用.方法:采用Morris水迷宫的程序研究大鼠的空间记忆,利用开场实验方法测定动物自发活动量.结果:在水迷宫的学习过程中,腹腔内注射东莨菪碱(0.4mg/kg,ip)明显延长大鼠上台的潜伏期,而腹腔内注射TAK-147或donepezil(多奈哌齐)能剂量依赖性地改善东莨菪碱诱发的记忆损伤,两药在0.1-1.0mg/kg的剂量时具有显著性差异.在记忆的再生过程中,腹腔内注射东莨菪碱(1.5mg/kg,ip)引起空间记忆再生过程的障碍分别被TAK-147(0.1,0.3和1.0mg/kg)、多奈哌齐(0.3和1.0mg/kg)以及他克林(3和5mg/kg)显著性改善.TAK-147的作用比多奈哌齐略强却明显强于他克林.此外,在开场实验中,TAK-147和多奈哌齐与生理盐水和东莨菪碱相比,对大鼠运动量未产生明显改变.结论:TAK-147在空间认知功能上起重要的作用,进一步证明TAK-147能够成为一个治疗阿尔采默病的理想的胆碱酯酶抑制药.     

Chelation therapy improves spatial learning and memory impairment in gallium arsenide intoxicated rats

The chelation potency of Desferrioxamine (DFO), Deferiprone (L₁) and Deferasirox (Ex) to improve spatial learning and memory impairment was investigated in gallium arsenide (20?mg/kg) exposed rats. After the chelation therapy, the Morris water maze test was performed and the rats were sacrificed and brains were sampled for determination of gallium and arsenic ions by ICP-OES. The results showed that the distance traveled and escape latency to find the platform in three consecutive blocks significantly increased after exposure to gallium arsenide. Moreover these parameters significantly decreased in the probe test. Whereas administration of chelators significantly improved memory performance in chelating therapy groups. Also, the results showed that the concentration of gallium and arsenic in the brain tissue after chelating therapy significantly decreased. Our results suggest that chelators are able to compensate the learning and memory impairments, probably due to the disposal of gallium and arsenic from the brain tissue.     

Facilitating effect of histamine on spatial memory deficits induced by dizocilpine as evaluated by 8-arm radial maze in SD rats

AIM: To investigate whether or not histamine is involved in spatial memory deficits induced by dizocilpine (MK-801) as evaluated by 8-arm radial maze of rats. METHODS: 8-Arm (4-arm baited) radial maze was used to measure spatial memory in rats. RESULTS: Bilaterally intrahippocampal (ih) injection of MK-801 (0.3 μg/site) impaired working memory and reference memory in rats. Both histamine (50, 100 ng/site, ih) and intraperitoneal (ip) injection of histidine (100, 200 mg/kg) markedly improved the spatial memory deficits induced by MK-801. On the other hand, the ameliorating effect of histidine (100 mg/kg, ip) was completely antagonized by α-fluoromethylhistidine (α-FMH, 5 μg/site, ih), a potent and selective histidine decarboxylase (HDC) inhibitor, and H_1-antagonist pyrilamine (1 μg/site, ih), but not by H_2-antagonist cimetidine, even at a high dose (2.5 μg/site, ih). CONCLUSION: The hippocampal histamine plays an important role in the ameliorating effect on MK-801-induced spatial memory deficits,     

Oxymatrine attenuates diabetes-associated cognitive deficits in rats

Aim： Oxymatrine （OMT） is the major quinolizidine alkaloid extracted from the root of Sophora flavescens Ait （the Chinese herb Kushen） and exhibits diverse pharmacological actions. In this work we investigated the effects of OMT on diabetes-associated cognitive decline （DACD） in a rat model of diabetes and explored the mechanisms of action. Methods： Male Wistar rats were injected with streptozotocin （65 mg/kg, ip） once to induce diabetes. The rats were then treated with vehicle or OMT （60 or 120 mg/kgper day, ip） for 7 weeks. Memory function was assessed using Morris water maze test. The levels of malondialdehyde （MDA）, superoxide dismutase （SOD）, glutathione （GSH）, NF-KB p65 unit, TNF-a, IL-113 and caspase-3 in the cerebral cortex and hippocampus were quantified. Results： The diabetic rats exhibited markedly reduced body weight and increased plasma glucose level. The memory function of the rats assessed using Morris water maze test showed significant reduction in the percentage of time spent in the target quadrant and the number of times crossing the platform, coupled with markedly prolongation of escape latency and mean path length. Moreover, the rats showed oxidative stress （significantly increased MDA, decreased SOD and reduced GSH levels）, as well as significant increases of NF-KB p65 unit, TNF-（x, IL-113 and caspase-3 lew.~ls in the cerebral cortex and hippocampus. Chronic treatment with OMT dose- dependently reversed these behavioral, biochemical and molecular changes in the diabetic rats. However, the swimming speed had no significant difference among the control, diabetic and OMT-treated diabetic rats. Conclusion： Chronic treatment with OMT alleviates diabetes-associated cognitive decline in rats, which is associated with oxidative stress, inflammation and apoptotic cascades.     

硫化氢通过抗氧化作用改善脑缺氧导致的小鼠空间记忆障碍(英文)

目的观察外源性H2S对缺氧性脑损伤小鼠空间学习记忆障碍的影响,并探究其作用机制。方法连续4 d sc给予NaNO2 120 mg.kg-1.d-1制备缺氧模型;氢硫化钠(NaHS)治疗组在制备模型的同时ip给予NaHS 1 mg.kg-1.d-1。每天给药前进行Morris水迷宫实验,测定逃避潜伏期、原平台象限停留时间和穿越平台次数。比色法检测小鼠脑组织中超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量。HE染色观察海马组织切片CA1区神经元形态学改变。结果水迷宫实验第3天和第4天,模型组小鼠逃避潜伏期分别为(26.0±7.3)s和(23.3±8.7)s,明显长于正常对照组的(16.1±9.6)s(P<0.05)和(11.1±6.2)s(P<0.01)。第5天,模型组小鼠穿越平台次数为4.1±1.9,在原平台象限停留时间为(20±8)s,与正常对照组穿越平台次数(7.2±1.6)次和在原平台象限停留时间(28±8)s比较明显减少(P<0.01)。与正常对照组相比,模型组小鼠脑组织中SOD活性降低12.6%(P<0.01),MDA含量升高43.9%(P<0.01)。在模型组小鼠海马CA1区,锥体细胞出现明显的核固缩、胞浆深染和排列紊乱等变性改变。与模型组比较,NaHS组小鼠在水迷宫实验的第3天和第4天逃避潜伏期明显缩短(P<0.05),分别为(17.9±7.0)s和(15.8±8.5)s;在平台所在象限停留时间和穿越平台次数明显增加(P<0.01),分别为(30±9)s和(6.7±2.5)次;SOD活性升高了8.9%(P<0.05),MDA含量显著下降了29.6%(P<0.01);海马CA1区神经元变性改变较模型组得到显著缓解。结论 NaHS减轻了脑缺氧损伤诱发的小鼠学习记忆的损害,其作用机制可能与H2S衰减海马区神经元损伤和抗氧化作用有关。     

Noggin反义寡核苷酸对大鼠空间学习与记忆的影响

目的：研究noggin反义寡核苷酸对大鼠空间学习与记忆的影响．方法：用原位杂交技术检测大鼠海马内noggin mRNA的表达,Morris水迷宫检测大鼠空间学习与记忆．结果：Morris水迷宫训练引起大鼠海马齿回(DG)与CA3区noggin mRNA阳性神经元数明显增多．侧脑室注射noggin反义寡核苷酸,不仅抑制Morris水迷宫训练引起的海马noggin mRNA阳性神经元数增多,同时阻滞学习与记忆的形成．正义noggin寡核苷酸无此效应．结论：Noggin作为一胚胎基因,表达于成年大鼠的海马,并与其空间学习记忆行为有关．     

组胺对东莨菪碱所致大鼠空间记忆障碍的改善作用(英文)

目的:研究和阐明中枢组胺对东莨菪碱所致大鼠(空间)记忆障碍的作用机制.方法:采用迷宫学习的程序研究大鼠的空间记忆,并利用高效液相法测定脑内组胺含量.结果:侧脑室内注射组胺(100,200 ng)、2-β-噻唑乙胺(200 ng)及4-[4’-(环己氨基硫代甲酰基哌啶)]-4H-咪唑(50μg)或腹腔内注射组胺酸(1000 mg/kg)均可对抗东莨菪碱所致的记忆障碍.相反,4-甲基组胺(50-200 ng)却无明显作用.组胺(200 ng)和组胺酸(1000 mg/kg)均可有效地增加大脑皮层、海马及下丘脑中的组胺含量.结论:中枢组胺可以明显改善东莨菪碱引起的大鼠空间记忆障碍,其作用主要与H_1、H_3受体相关.