人参皂苷Rg1脂质体对东莨菪碱诱导大鼠学习记忆障碍的改善及其作用机制

目的：观察人参皂苷Rg1脂质体（Rg1-L）对东莨菪碱诱导大鼠学习记忆障碍的改善，并探讨其相关机制，方法：制备东莨菪碱诱导大鼠学习记忆障碍模型。采用Y型迷宫评价Rg1-L对模型大鼠学习记忆的影响，并测定大鼠大脑皮质中乙酰胆碱酯酶活性。结果：Rg1-L可以显著改善模型大鼠学习记忆功能。同时抑制大脑皮质中乙酰胆碱酯酶活性。结论：Rg1-L对东莨菪碱诱导大鼠学习记忆障碍模型大鼠的学习记忆功能有显著的改善作用，其机制可能与抑制大脑皮质中乙酰胆碱酯酶活性、提高人参皂苷Rg1生物利用度有关。     

Age-related impairment in learning but not memory in SAMP8 female mice

Four-month and 12-month-old SAM (Senescence Accelerated Mouse)-P8 and -R1 female mice, either intact or ovariectomized, were trained to avoid foot shock in a T-maze. Mice were trained until they made their first avoidance. Memory retention of this task was then tested 1 week later. The results indicated that P8, but not R1, female mice whether intact or ovariectomized, showed an age-related learning impairment. This impairment was more apparent in ovariectomized mice, as ovariectomy was associated with a significant reduction in the mean trials to make an avoidance in all groups except 12-month P8 females. Of greatest interest was the absence of any age-related impairment of retention in P8 females. In several previous studies, SAM-P8, but not R1, males showed an age-related impairment of learning and memory. These results indicate that age-related impairment of memory in P8 mice may be inherited in a sex-related manner, and suggests that the mechanisms involved in the development of impaired learning and memory are different.     

海马补肾丸对小鼠学习记忆障碍的改善作用

目的考察海马补肾丸对小鼠学习记忆障碍的改善作用,并探讨其作用机制。方法小鼠随机分为对照组、模型组、吡拉西坦组、龟龄集组和海马补肾丸组。采用腹腔注射东莨菪碱制备小鼠记忆获得性障碍模型,计算学习正确率,测定蛋白含量和乙酰胆碱酯酶活力。采用腹腔注射亚硝酸钠制备小鼠记忆巩固性障碍模型,计算训练、测定学习正确率,测定蛋白含量、去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)以及丙二醛(MDA)、超氧化物歧化酶(SOD)含量。结果海马补肾丸2.20 g/kg组能显著增加小鼠学习记忆的正确率(P0.05),显著降低乙酰胆碱酯酶活力(P0.01)。测定时,与模型组比较,海马补肾丸1.10、2.20 g/kg组能显著增加小鼠学习记忆正确率(P0.05),能不同程度增加小鼠大脑SOD含量,降低MDA含量(P0.05、0.01)。结论海马补肾丸能明显改善小鼠的记忆获得、记忆巩固障碍,推测其作用机制主要是通过降低乙酰胆碱酯酶活性,增加脑内乙酰胆碱的含量,改善记忆获得能力;通过抗脑组织的氧化损伤,增加大脑SOD含量,降低MDA含量,改善记忆巩固能力。     

中药海龙抗D-半乳糖诱导衰老小鼠学习记忆损伤作用研究

目的 研究中药海龙对D-半乳糖诱导衰老小鼠学习记忆损伤的影响及其作用机制。方法 采用高效液相色谱（HPLC）技术测定海龙中抗学习记忆损伤有效成分二十二碳六烯酸（DHA）含量;腹腔注射D-半乳糖(D-gal)制备衰老小鼠模型,以Morris水迷宫实验及蛋白免疫印迹法等,对小鼠学习记忆能力、海马组织氧化损伤相关生化指标及蛋白表达进行检测,探究海龙对衰老小鼠学习记忆损伤的保护作用及其机制。结果 HPLC结果显示,海龙中DHA含量为7.761 3 mg/g（以生药计）,约占总成分的47%;Morris水迷宫实验结果显示,海龙可减少学习记忆损伤小鼠逃避潜伏期时间,增加小鼠目标象限游泳时间、游泳路程占比、穿台次数,改善小鼠学习记忆损伤;此外,海龙可激活衰老小鼠海马组织AKT/FOXO1/SOD2信号通路,上调氧化应激通路相关蛋白表达,降低衰老小鼠海马组织氧化损伤程度改善小鼠学习记忆损伤。结论 本研究发现海龙富含二十二碳六烯酸,具有改善D-半乳糖诱导衰老小鼠学习记忆损伤的作用,并初步阐明其作用机制与抗氧化相关,为中药海龙抗学习记忆损伤研究提供了实验依据。     

苯氧茚酮类衍生物的保护神经细胞和改善小鼠学习记忆作用

目的观察新型乙酰胆碱酯酶抑制剂苯氧茚酮类衍生物(YKY-1~7)对谷氨酸诱导PC12细胞神经毒性的保护作用和对Aβ25~35致痴呆小鼠学习记忆能力的改善作用。方法2mmol·L-1谷氨酸诱导PC12细胞兴奋毒性损伤,观察YKY-1~7对谷氨酸致PC12细胞兴奋毒性的保护作用;小鼠侧脑室注射(icv)凝聚态Aβ25~358μg制作痴呆模型,次日,igYKY-72·5、5、10mg·kg-1,连续10d,测试小鼠被动回避的学习记忆能力,大脑皮层、海马和血清中的乙酰胆碱酯酶(AChE)活性以及大脑皮层局部脑血流量。结果7个苯氧茚酮类衍生物中有6个对谷氨酸诱导的PC12细胞兴奋毒性损伤具有较好的保护作用,其中YKY-7的作用最强。YKY-7可明显改善Aβ25~35所致痴呆小鼠的学习记忆能力,对皮层和海马组织中AChE活性有相对较弱的选择性抑制作用,对皮层局部脑血流量也有一定的提高作用。结论所合成的多数苯氧茚酮类衍生物对神经细胞具有保护作用;对Aβ25~35icv致痴呆模型小鼠学习记忆功能有较大的改善作用,其作用可能与一定程度的选择性抑制大脑皮层和海马AChE活性有关。     

Vortioxetine,but not escitalopram or duloxetine,reverses memory impairment induced by central 5-HT depletion in rats: Evidence for direct 5-HT receptor modulation

Depressed patients suffer from cognitive dysfunction, including memory deficits. Acute serotonin (5-HT) depletion impairs memory and mood in vulnerable patients. The investigational multimodal acting antidepressant vortioxetine is a 5-HT₃, 5-HT₇ and 5-HT_1D receptor antagonist, 5-HT_1B receptor partial agonist, 5-HT_1A receptor agonist and 5-HT transporter (SERT) inhibitor that enhances memory in normal rats in novel object recognition (NOR) and conditioned fear (Mørk et al., 2013). We hypothesized that vortioxetine's 5-HT receptor mechanisms are involved in its memory effects, and therefore investigated these effects in 5-HT depleted rats. Four injections of the irreversible tryptophan hydroxylase inhibitor 4-chloro-dl-phenylalanine methyl ester hydrochloride (PCPA, 86 mg/kg, s.c.) induced 5-HT depletion, as measured in hippocampal homogenate and microdialysate. The effects of acute challenge with vortioxetine or the 5-HT releaser fenfluramine on extracellular 5-HT were measured in PCPA-treated and control rats. PCPA's effects on NOR and spontaneous alternation (SA) performance were assessed along with the effects of acute treatment with 5-hydroxy-l-tryptophan (5-HTP), vortioxetine, the selective 5-HT reuptake inhibitor escitalopram, or the 5-HT norepinephrine reuptake inhibitor duloxetine. SERT occupancies were estimated by ex vivo autoradiography. PCPA depleted central 5-HT by >90% in tissue and microdialysate, and impaired NOR and SA performance. Restoring central 5-HT with 5-HTP reversed these deficits. At similar SERT occupancies (>90%) vortioxetine, but not escitalopram or duloxetine, restored memory performance. Acute fenfluramine significantly increased extracellular 5-HT in control and PCPA-treated rats, while vortioxetine did so only in control rats. Thus, vortioxetine restores 5-HT depletion impaired memory performance in rats through one or more of its receptor activities.     

Low-dose oral lorazepam administration in Alzheimer subjects and age-matched controls

Ten patients with Alzheimer's disease and ten age-matched normal controls were studied in a double-blind, placebo-controlled acute trial of 1 mg PO lorazepam to test the effects of low-dose benzodiazepine on memory and behavior in a mostly older population. Cognitive effects differed somewhat between Alzheimer patients and normal controls, with Alzheimer patients revealing predominantly attentional impairments and age-matched controls showing possible disinhibition. Specifically, Alzheimer patients made more omission errors on a continuous performance task, whereas controls made more commission and intrusion errors with lorazepam versus placebo. This low dose of lorazepam (1 mg), which was associated with mild but statistically significant sedation in both groups, also produced no significant decrease in recent memory or in access to semantic memory. These cognitive findings contrast markedly to the reported effects of scopolamine on recent memory; therefore, supporting the idea that cholinergic interruption has a more specific effect on human memory and on learning than that of low-dose benzodiazepines. Further studies with a wider dose range of benzodiazepines are necessary to evaluate the possibility of differential sensitivity between Alzheimer patients and normal elderly controls.     

Memory enhancement induced in chicks by anesthetic doses of chlorpromazine

Three experiments describe retroactive memory enhancement in chicks by chlorpromazine (CPZ), a potent membrane stabilizer at anesthetic doses. First, chicks trained on a one-trial peck suppression task under moderate aversant conditions and given 60–144 mg CPZ/kg, intraperitoneally, displayed increased memory retention 24 h later when compared with chicks given saline or 15–36 CPZ/kg. The second experiment confirmed the memory enhancement using a different moderate aversant on a different peck target and extended the effect to 48 h. The third experiment demonstrated the CPZ effect to be retrograde because the enhancement observed when CPZ was injected 1 min or 3 min after training did not occur when injection was delayed 4 h. One speculative interpretation of retrograde enhancement with CPZ includes the stabilization of swollen dendritic spines, which may facilitate neuronal pathways.     

Phenserine: a physostigmine derivative that is a long-acting inhibitor of cholinesterase and demonstrates a wide dose range for attenuating a scopolamine-induced learning impairment of rats in a 14-unit T-maze

Phenserine ((–)-N-phenylcarbamoyl eseroline), a carbamate analog of physostigmine (Phy), is a long-acting inhibitor of cholinesterase. We have assessed the potential clinical value of phenserine for cholinomimetic therapy of cognitive impairments associated with aging and Alzheimer's disease by evaluating its duration of in vivo activity against rat plasma acetylcholinesterase (AChE) and its effect on attenuating a scopolamine-induced impairment in learning performance of young rats in a shock-motivated 14-unit T-maze. Phenserine achieved maximum AChE inhibition of 73.5% at 5 min and maintained a high and relatively constant inhibition for more than 8 h. For analysis of effects on learning performance, 69, 3-month-old male Fischer-344 rats were pretrained in a straight runway to avoid electric footshock. On the following day, each animal received 15 trials in the 14-unit T-maze. Sixty minutes prior to the maze training, each rat received the first IP injection of either vehicle (Tween 80, ethanol and 0.9% NaCl) or phenserine at 1.5, 3.0, 4.0, 5.0, 7.5, or 10.0 mg/kg. Then 30 min prior to the training, each animal received a second IP injection of either 0.9% NaCl or scopolamine hydrochloride (0.75 mg/kg; SCOP). Compared to the vehicle-SCOP group, all but the 7.5 mg/kg dose of phenserine significantly ameliorated error performance, runtime, shock frequency and shock duration in SCOP-treated rats at the final block of three trials. Appearing to have a long effect and a wide therapeutic window, phenserine deserves further study as a cognitive enhancer.     

轻度认知功能障碍与阿尔茨海默病患者血管危险因素的研究

目的 探讨血管危险因素与轻度认知功能障碍（Mild cognitive impairment,MCI）及阿尔茨海默病（Alzheimer＇sdisease,AD）的关系,并进一步分析各因素与认知功能下降程度的相关性.方法 选择2012年6月至2014年6月于门诊及住院部诊断为MCI及AD的患者各35例,同期体检的性别、年龄、文化程度相匹配的健康老人35例为对照.所有研究对象均进行MMSE、ADAS-Cog量表评定,采集晨空腹血进行血脂、血糖检测,并分别记录性别、年龄、身高、体重、吸烟、饮酒等情况.采用最小显著性差异法（LSD）比较各组间血管危险因素的差异、Pearson＇s相关分析各因素与认知功能评分的相关性.结果 与对照组相比,MCI组、AD组体重指数、血胆固醇水平呈进行性下降,但仅AD组与对照组相比差异有统计学意义.收缩压水平MCI组、AD组与对照组相比均明显升高,MCI组与AD组比较差异亦有统计学意义.Pearson＇s分析可见各因素与认知功能下降程度之间呈线性相关.糖尿病、饮酒比率AD组与对照组相比亦明显升高.结论 血管危险因素在老年人认知功能下降过程中有重要的作用,并有可能指导AD早期诊断及治疗.     

小鼠暂时性脑缺血引起学习记忆障碍模型的制备及人参皂甙的保护作用

人参皂甙是人参的主要有效成分。本文在建立小鼠脑缺血再灌注导致学习记忆障碍模型的基础上，用跳台、避暗两种实验方法观察了人参皂甙对小鼠脑缺血再灌注后学习记忆功能的保护作用。结果显示小鼠脑缺血再灌注可以导致学习记忆障碍，而人参皂甙（１０，１００ｍｇ·ｋｇ－１，ｐｏ）可以对这种记忆障碍起到保护作用。     

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。     

芍药苷对D-半乳糖和亚硝酸钠诱导的小鼠认知障碍与神经元变性的改善作用

目的:探讨芍药苷(PF)对D-半乳糖(D-gal)和亚硝酸钠(NaNO2)诱导的衰老小鼠认知障碍与神经元凋亡的改善作用.方法:皮下注射D-gal和NaNO2制备小鼠衰老模型.使用Morris水迷宫检测小鼠空间记忆能力.取小鼠脑组织检测丙二醛(MDA)水平、总超氧化物歧化酶(T-SOD)和谷胱甘肽过氧化酶(GSH-Px)活性.经H&E、TUNEL染色和caspase-3免疫组化染色观察海马神经元损伤、凋亡和caspase-3表达变化.结果:D-gal和NaNO2可诱导小鼠认知功能衰退,海马神经元损伤.给予PF可改善模型鼠认知障碍和海马神经元损伤,减少caspase-3在海马的表达,提高降低的T-SOD、GSH-Px活性,减少升高的MDA含量.结论:PF通过抑制氧化损伤途径改善D-gal和NaNO2诱导的小鼠认知障碍与海马神经元变性.     

祁州漏芦乙醇提取物对D-半乳糖所致衰老小鼠学习记忆的影响

目的研究漏芦乙醇提取物对D 半乳糖所致衰老小鼠学习记忆的影响以及对脑组织中过氧化脂质及脂褐质含量的影响。方法采用一次性被动回避式条件反射的方法 (跳台法及避暗法 )测定动物的学习记忆能力 ,用生化学方法测定脑组织过氧化脂质及脂褐质含量。结果漏芦乙醇提取物剂量依赖性地减少D 半乳糖致衰老小鼠跳台及避暗错误反应次数并延长错误反应潜伏期 ;显著减少衰老小鼠脑组织中过氧化脂质及脂褐质的含量。结论实验结果提示漏芦乙醇提取物具有抗衰益智作用。其改善记忆障碍作用可能与抗自由基过氧化 ,减少脑组织中过氧化脂质及脂褐质生成有关     

Transfer of learning to compensate for impairment by alcohol and visual degradation

Rationale Past research on social drinkers shows that prior experience performing a task in a visually degraded environment results in the reduction of alcohol-induced impairment. It is possible that task experience under alcohol might similarly carry over to reduce impairment from visual degradation. Objectives The purpose of this study was to test the symmetry of the transfer of learning between two distinct sources of impairment, visual degradation and alcohol. Materials and methods Psychomotor impairment was measured by a pursuit rotor tracking task. Forty two participants were randomly assigned to one of six treatment groups. Two groups were tested under alcohol after having prior task experience performing with or without visual degradation. Two groups were tested under visual degradation after having prior task experience performing under active (0.65 g/kg) or inactive (placebo) doses of alcohol. The remaining two groups served as controls that tested the learning effects of repeating each active treatment. Results Clear evidence for asymmetrical transfer of learning was observed. Prior task experience with visual degradation reduced the impairing effects of alcohol. By contrast, prior task experience under alcohol had no effect on impairment produced by visual degradation. Conclusions Evidence for differential transfer of learning to compensate for alcohol- and visual-degradation-induced impairment is of practical interest, given that the two disturbances commonly co-occur outside the laboratory. Reasons for the asymmetry are unclear, and likely involve differences in mechanisms by which each treatment impairs psychomotor function.     

Memory enhancement: Supra-additive effect of subcutaneous cholinergic drug combinations in mice

The amnesias characteristic of Alzheimer's disease and other age-related dementias are refractory to conventional pharmacotherapy. a recent treatment strategy is to combine present drugs to improve their memory enhancing effect. We used mice weakly trained on active avoidance in a T-maze to compare the effect of cholinergic drugs, given alone and in two-drug combinations, on retention test performance. All drugs were injected SC immediately after training. Memory retention was tested 1 week later. A dose-response curve was determined for each of four drugs (arecoline, edrophonium, oxotremorine, tacrine) and for each of the six possible two-drug combinations. Each drug and each combination improved retention test performance up to an optimal dose; the improvement decreased with further increases in dose. A striking reduction (66.2%–95.7%) in the optimal dose for enhanced retention was observed with these two-drug combinations.     

梓醇对D-半乳糖致亚急性衰老小鼠学习记忆及脑中相关抗氧化酶活性的影响

目的观察梓醇对D-半乳糖(D-gal)致亚急性衰老小鼠学习记忆及脑组织中相关抗氧化酶活性的影响。方法用D-gal皮下注射制备衰老小鼠模型,同时在前两周和后两周分别皮下注射给予梓醇(2.5 mg/kg),检测小鼠学习记忆能力和大脑皮层、海马中丙二醛(MDA)水平,超氧化物岐化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)活性。结果衰老模型组小鼠空间学习记忆能力下降,逃避潜伏期较正常对照组明显延长,脑中SOD、GSH-PX活性降低,MDA含量增高。给予梓醇预防和治疗后可以改善衰老模型小鼠的学习记忆能力,并显著提高脑中SOD、GSH-PX活性,降低MDA水平。结论梓醇可改善D-gal致衰老小鼠的学习记忆障碍,此作用可能与梓醇的抗氧化作用有关。     

柚皮苷改善CCL2所致大鼠学习记忆障碍及其机制

目的探究柚皮苷改善CCL2诱导大鼠学习记忆障碍及其机制。方法56只SD大鼠随机分为空白组、假手术组、模型组(CCL2)、阳性药(CCL2+memantine)组、柚皮苷低(CCL2+25 mg·kg^-1柚皮苷)、中(CCL2+50 mg·kg^-1柚皮苷)、高(CCL2+100 mg·kg^-1柚皮苷)剂量组。除空白、假手术组外,各组均通过脑部定位将CCL2注射至大鼠海马制作学习记忆障碍模型。Morris水迷宫检测各组大鼠的学习和记忆水平;HE染色观察大鼠海马CA1区神经元形态;试剂盒检测海马SOD、GSH-PX活力和MDA含量;qRT-PCR检测凋亡基因caspase-3、caspase-8、Bax、Bcl-2 mRNA的相对表达。结果与模型组相比,各柚皮苷给药组大鼠逃避潜伏期及游泳路程均明显减少,平台穿越次数增加;海马CA1区神经元排列紧密且形态良好;SOD、GSH-PX活力升高,MDA含量降低;凋亡基因caspase-8、caspase-3、Bax mRNA相对表达量减少;Bcl-2表达量增加。结论柚皮苷能明显改善CCL2所致大鼠学习记忆功能障碍,其机制与柚皮苷的抗氧化和抗凋亡效应有关。     

Metalloelastase (MMP-12) induced inflammatory response in mice airways: effects of dexamethasone, rolipram and marimastat

Direct instillation of a recombinant human form of MMP-12 (rhMMP-12) in mice airways elicited an early inflammatory response characterized by neutrophil influx, cytokine release and gelatinase activation followed by a delayed response, mainly characterized by macrophage recruitment. As this experimental model of lung inflammation partially mimics some features of chronic obstructive pulmonary disease (COPD), we have investigated the effects of treatment by anti-inflammatory compounds, dexamethasone and rolipram and a non-specific matrix metalloproteinase (MMP) inhibitor, marimastat. The compounds were administrated orally, 1 h before rhMMP-12 instillation (8 x 10(-3) U/mouse). Total and differential cell counts were evaluated in the bronchoalveolar lavage fluids. Cytokines and MMP-9 were quantified in bronchoalveolar lavage fluids and in lung homogenate supernatants. Marimastat (100 mg/kg), dexamethasone (10 mg/kg) and rolipram (0.1 and 0.3 mg/kg) were able to decrease significantly neutrophil recruitment at 4 and 24 h after rhMMP-12 instillation, but only marimastat (30 and 100 mg/kg) was effective at decreasing the macrophage recruitment occurring at day 7. Marimastat (100 mg/kg), dexamethasone (10 mg/kg) and rolipram (0.3 mg/kg) reduced significantly IL-6, KC/CXCL1, MIP-1alpha/CCL3 and MMP-9 levels in bronchoalveolar lavage fluid. Similar results were obtained in lung homogenates except with rolipram. Dexamethasone and rolipram were able to inhibit the early inflammatory response but were ineffective to limit the macrophage influx. In contrast, marimastat was able to reduce early and late response. These data indicate that MMP-12 instillation in mice could highlight some of the inflammatory response seen in COPD and could be used for the pharmacological evaluation of new anti-inflammatory mechanisms of action.     

吡格列酮改善脑室注射链脲霉素诱导的小鼠认知损害及其机制的研究

目的:研究吡格列酮对脑室注射链脲霉素诱导小鼠认知损害的影响及其作用机制。方法:采用双侧脑室注射链脲霉素(0.5 mg/kg)制备小鼠认知损害模型,吡格列酮连续灌胃给药20 d,每天1次,采用Morris水迷宫和Y迷宫试验评价认知功能,并测定脑内乙酰胆碱(Ach)、乙酰胆碱酯酶(AchE)、乙酰胆碱转移酶(ChAT)以及外周血糖水平。结果:吡格列酮(9 mg.kg-1.d-1,18 mg.kg-1.d-1)能显著缩短小鼠在可见平台试验中寻找平台的潜伏期,增加空间探索试验中平台所在象限停留时间百分率;增加Y迷宫测试中的正确反应次数。吡格列酮还能显著增加小鼠脑组织海马区和皮层区Ach含量,降低AchE活性,并且增加ChAT活性,但对动物外周血糖无明显影响。结论:吡格列酮可通过降低AchE活性和提高ChAT活性,使小鼠脑内Ach含量增加,从而改善脑室注射链脲霉素所致的小鼠认知损害。