定志小丸对D-半乳糖致衰老模型小鼠学习、记忆能力及抗氧化活性的影响

目的研究定志小丸对D-半乳糖所致亚急性衰老小鼠学习记忆能力和脂质过氧化的影响.方法小鼠背部皮下注射D-半乳糖造成早衰模型,采用跳台法测小鼠学习记忆能力,血清和脑组织SOD、MDA.结果定志小丸使致D-半乳糖衰老小鼠跳台错误潜伏期显著延长,错误次数显著减少,血清和脑组织SOD 活力提高,MDA含量降低.结论定志小丸能改善D-半乳糖致衰小鼠的学习记忆功能,其机制可能与降低脑组织中脂质过氧化物的含量有关.     

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。     

定志小丸对 D-半乳糖致衰老模型小鼠学习、记忆能力及抗氧化活性的影响

目的研究定志小丸对D-半乳糖所致亚急性衰老小鼠学习记忆能力和脂质过氧化的影响。方法小鼠背部皮下注射D-半乳糖造成早衰模型，采用跳台法测小鼠学习记忆能力，血清和脑组织SOD、MDA。结果定志小丸使致D-半乳糖衰老小鼠跳台错误潜伏期显著延长，错误次数显著减少，血清和脑组织SOD 活力提高，MDA 含量降低。结论定志小丸能改善D-半乳糖致衰小鼠的学习记忆功能，其机制可能与降低脑组织中脂质过氧化物的含量有关。     

十全大补汤对D-半乳糖模型小鼠学习记忆及抗氧化的研究

目的十全大补汤对D-半乳糖致衰老小鼠学习记忆能力及抗氧化作用的研究。方法连续给小鼠注射D-半乳糖6周,同时从第三周起给模型鼠灌胃十全大补汤,给药结束后,进行学习记忆行为测定,采血清测定超氧化歧化酶（SOD）、丙二醛（MDA）含量。结果十全大补汤组小鼠的学习、记忆获得和记忆消退的错误次数明显少于衰老模型组（P〈0．05）;与模型组比较,十全大补汤组小鼠血清SOD活性显著性降低。结论十全大补汤能改善D-半乳糖致衰老小鼠的学习记忆能力,提高体内SOD活性,增强其对自由基的清除能力,抑制脂质过氧化作用。     

芹菜籽油抗D-半乳糖致衰老模型动物的作用研究

目的:研究芹菜籽油(CSO)抗D-半乳糖致衰老模型动物的作用。方法:分别对小鼠和大鼠皮下注射D-半乳糖复制衰老模型,同时灌胃给予CSO。6周后,通过跳台法和电生理方法观察CSO对衰老模型动物学习记忆的改善,同时比较衰老小鼠脑组织内丙二醛(MDA)含量及单胺氧化酶B(MAO-B)、超氧化物歧化酶(SOD)活性的差异。结果:CSO对衰老动物的学习记忆障碍有显著的改善作用;能显著降低衰老小鼠脑组织内MDA的含量和MAO-B的活性,增加SOD的活性。结论:CSO具有较好的抗衰老作用     

火麻仁油对D-半乳糖致衰老小鼠学习记忆障碍的保护作用研究

目的:研究火麻仁油对D-半乳糖(D-gal)致衰老小鼠学习记忆能力的保护作用,并探讨其作用机制.方法:采用D-半乳糖诱导小鼠衰老模型,用跳台法、水迷宫法和Morris水迷宫法测定衰老小鼠学习记忆能力,检测小鼠脑组织丙二醛(MDA)含量和总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性及大脑皮层和海马组织中乙酰胆碱(Ach)含量和乙酰胆碱酯酶(AchE)、胆碱乙酰化转移酶(ChAT)活性,观察脑组织组织形态学变化.结果:火麻仁油(3、6和12 mL/kg)能明显延长跳台实验的跳台潜伏期,缩短错误次数;缩短水迷宫实验达到时间和减少错误次数;缩短Morris水迷宫实验逃避潜伏期和第1次到达原平台时间,增加穿越原平台次数和逗留时间;能显著增加脑组织中T-AOC、SOD、GSH-Px活性和降低MDA含量,增加大脑皮层和海马组织中Ach含量和AchE、ChAT活性,减轻脑组织损伤.结论:火麻仁油可显著改善D-半乳糖致衰老小鼠学习记忆能力,其机制可能与其提高脑组织抗氧化和清除自由基能力,增强中枢胆碱能神经系统功能有关.     

延胡索总生物碱对D-半乳糖所致衰老模型小鼠相关指标的影响

目的探讨延胡索总生物碱(YHS)对D-半乳糖所致衰老模型小鼠相关指标的影响。方法以D-半乳糖所致衰老小鼠为实验动物,检测小鼠的学习记忆能力及脑组织中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、乙酰胆碱转移酶(ChAT)、乙酰胆碱酯酶(AChE)的活性。结果延胡索总生物碱能使D-半乳糖所致衰老模型小鼠记忆恢复正常,能升高脑组织中SOD、CAT、ChAT的含量,降低AChE的含量。结论延胡索总生物碱有抗衰老的作用。     

裂褶菌胞外多糖对D-半乳糖致衰老小鼠学习记忆及代谢产物的影响

目的研究裂褶菌(Schizophyllum commne Fr)胞外多糖(SPG)对D-半乳糖致衰老小鼠各项指标的影响。方法建立D-半乳糖衰老小鼠模型,以其学习记忆成绩,免疫器官指数,血清、肝、脑中超氧化物歧化酶(SOD)活力、丙二醛(MDA)含量,脑中单胺氧化酶(MAO)活力,肝、脑细胞线粒体DNA含量为指标,对SPG的抗衰老作用进行研究。结果与模型组比较,SPG可恢复D-半乳糖致衰老小鼠的学习记忆能力;拮抗免疫器官萎缩;提高其血清、肝和脑中SOD活性;减少MDA在体内积累;抑制脑中MAO活性;降低肝、脑细胞线粒体DNA相对含量。最适剂量为200 mg.kg-1。结论高剂量SPG具有明显抗衰老作用(P<0.01),且具有靶向性,对血清和肝组织的抗衰老作用较强,对大脑的改善作用不如前者。     

花椒多酚类化合物对衰老小鼠记忆障碍的改善作用

目的探讨花椒多酚类化合物总提取物（ZPPC）对D-半乳糖致衰老模型小鼠学习记忆能力及抗氧化能力的影响。方法模型组,ZPPC低、中、高剂量组和阳性对照组皮下注射10%D-半乳糖6周建立衰老小鼠模型,ZPPC低、中、高剂量组同时灌胃给予ZPPC,正常对照组和模型组给予等量的生理盐水,阳性对照组同时灌胃给予维生素E。用Morris水迷宫实验检测小鼠的学习记忆能力,同时检测小鼠脑组织超氧化物歧化酶（SOD）活力以及丙二醛（MDA）含量。结果与正常对照组比较,模型组小鼠学习记忆能力降低,脑组织SOD活力下降,MDA含量增加,均有统计学差异（P〈0.01）。灌胃给予高中低不同剂量的ZPPC后,小鼠上述变化明显改善,与模型组比较有统计学差异（P〈0.05或P〈0.01）。结论 ZPPC可改善D-半乳糖衰老模型小鼠的学习记忆能力,其作用机制可能与ZPPC具有抗氧化能力有关。     

茶多酚抗D-半乳糖诱致衰老小鼠脂质过氧化作用的研究

目的：观察D-半乳糖引起小鼠脂质过氧化作用及茶多酚的对抗作用。方法：通过测定血清和脑内SOD活性和MDA含量的变化。结果：D-半乳糖可引起小鼠血清和脑内SOD活性降低和MDA含量升高，而茶多酚可以升高SOD活性和降低MDA含量。结论：茶多酚对D-半乳糖致衰老小鼠血清和脑组织SOD活性降低，MDA含量升高有对抗作用。     

Saponins from Panax japonicus ameliorates cognition deficits and attenuates oxidative damage in D-galactose-induced brain aging of mice

Aging is an inevitable process featured by intelligence decline,behavioral disorders and cognitive disability.Increasing evidence indicates that oxidative stress plays a key role in the senescent development.Our previous study demonstrated that Saponins from Panax japonicus has a significant anti-oxidative effect in vitro.So the aim of the present study was to investigate the brain protective role of Saponins from Panax japonicus and its underlying mechanism.Mice were subcutaneously injected with D-galactose(D-gal,150 mg·kg-1·d-1) for 8 weeks and administered Saponins from Panax japonicus simultaneously.After 8 weeks of treatment,the animal behavior was observed in the open field test and water maze test,and the morphology of hippocampus was detected.The activities and mRNA expressions of antioxidant enzymes as well as the level of malondialdehyde(MDA) were evaluated.The extent of apoptosis was examined by TUNEL assay.The results indicate that Saponins from Panax japonicus markedly ameliorates the D-gal induced learning and memory impairment in both open field test and Morris water maze.Biochemical examination and RT-PCR method revealed that Saponins from Panax japonicus significantly increases the decreased activities and mRNA expressions of superoxide dismutase(SOD),catalase(CAT) and glutathione peroxidase(GSH-Px) and decreases the raised malondialdehyde(MDA) content in the serum and brain of aging mice induced by D-gal.Furthermore,Saponins from Panax japonicus significantly attenuates the D-gal-induced neuronal degeneration and apoptosis in the hippocampus.These results indicate that Saponins from Panax japonicus has a potential protect role on brain aging mice induced by D-gal and its mechanism,at least in part,via modification of the redox system in the organism.     

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.     

楠竹叶提取物对D-半乳糖诱导的小鼠认知损伤和氧化应激损伤的改善作用

目的：研究楠竹的竹叶提取物（bamboo leaf extracts,BLE）对D-半乳糖（D-galactose,D-gal）诱导的小鼠认知损伤和氧化应激损伤的改善作用。方法：32只小鼠随机分为对照组、D-gal组、BLE组（1 g·kg-1）和维生素E（VE）组（100 mg·kg-1）。D-gal组、BLE组和VE组采用皮下注射D-gal 50 mg·kg-1,每天一次,连续给药共8周造模。水迷宫实验检测小鼠学习记忆能力,同时测定海马中超氧化合物歧化酶（SOD）、过氧化氢酶（CAT）、丙二醛（MDA）、谷胱甘肽（GSH）的含量。免疫印迹法检测海马中突触后密度蛋白-95（PSD-95）和突触小泡蛋白（SYN）表达情况。结果：给予BLE饲料后,D-gal诱导的小鼠学习记忆损伤得到改善。脑组织中SOD、CAT和GSH的含量增加,MDA的含量减少。D-gal可降低海马中PSD-95和SYN的蛋白表达,而给予BLE饲料后,海马中PSD-95和SYN的蛋白表达增加。结论：BLE可改善D-gal诱导的小鼠学习记忆障碍和脑损伤。     

Ursolic acid ameliorates cognition deficits and attenuates oxidative damage in the brain of senescent mice induced by D-galactose

Ursolic acid (UA), a pentracyclic triterpene, is reported to have an antioxidant activity. Here we assessed the protective effect of UA against the d-galactose (D-gal)-induced neurotoxicity. We found that UA markedly reversed the D-gal induced learning and memory impairment by behavioral tests. The following antioxidant defense enzymes were measured: superoxide dismutases (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR). The content of the lipid peroxidation product malondialdehyde (MDA) was also analyzed. Our results indicated that the neuroprotective effect of UA against D-gal induced neurotoxicity might be caused, at least in part, by the increase in the activity of antioxidant enzymes with a reduction in lipid peroxidation. And UA also inhibited the activation of caspase-3 induced by D-gal. Furthermore, we found that UA significantly increased the level of growth-associated protein GAP43 in the brain of D-gal-treated mice. These results suggest that the pharmacological action of UA may offer a novel therapeutic strategy for the treatment of age-related conditions.     

A novel cyclic squamosamide analogue compound FLZ improves memory impairment in artificial senescence mice induced by chronic injection of D-galactose and NaNO2

The aim of the present study was to access the protective effect of a novel synthesized squamosamide cyclic analogue, compound FLZ, on memory impairment in artificially senescent mice induced by chronic injection of D-galactose and sodium nitrite (NaNO(2)). Artificially senescent mouse model was induced by consecutive injection of D-galactose (120 mg/kg) and NaNO(2) (90 mg/kg) once daily for 60 days. Compound FLZ (75 and 150 mg/kg) was orally administered once daily for 30 days after D-galactose and NaNO(2) injection for 30 days. The water maze test was used to evaluate the learning and memory function of mice. The content of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in serum were determined using different biochemical kits. The alterations in hippocampus morphology were assessed by light and electronic microscope. Immunoreactive cells of Bcl-2 in the hippocampus were counted by immunohistochemical staining, and Bcl-2 protein expression was analysed by Western blot method. The results indicate that injection of D-galactose and NaNO(2) induces memory impairment and neuronal damage in hippocampus of mice. In addition, serum SOD and GSH-Px activities decreased, while MDA level increased. Bcl-2-positive neurons and Bcl-2 protein expression in the hippocampus decreased remarkably. Oral administration of FLZ for 30 days significantly improved the cognitive deficits and the biochemical markers mentioned above, and also reduced the pathological alterations in mouse hippocampus. The results suggest that FLZ ameliorates memory deficits and pathological injury in artificially senescent mice induced by chronic injection of D-galactose and NaNO(2), indicating that FLZ is worth further studies for fighting antisenescence and dementia.     

Catalpol ameliorates cognition deficits and attenuates oxidative damage in the brain of senescent mice induced by D-galactose

The neuroprotective effects of catalpol, an iridoid glycoside isolated from the fresh Rehmannia roots, on the senescent mice induced by D-galactose were assessed. The mice subcutaneously injected with catalpol (5 or 10 mg/kg, 2 weeks, from fifth week) showed significantly improved learning and memory ability in Morris water maze test compared with d-galactose treated mice (150 mg/kg, 6 weeks). We further investigated the mechanism involved in the neuroprotective effects of catalpol on the mice brain tissue. The results showed that catalpol increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), decreased the malondialdehyde (MDA) level, elevated the activities of Na+ -K+ ATPase and Ca2+ -Mg2+ ATPase on the cerebral cortex and hippocampus of d-galactose treated mouse. All the data suggested that catalpol had the potential to be a useful cognitive impairment treatment, and its beneficial effects may be partly mediated via enhancing endogenous antioxidant enzymatic activities and inhibiting free radical generation.     

Ameliorative effect of lithium chloride against d-galactose induced behavioral and memory impairment,oxidative stress and alteration in serotonin function in rats

BackgroundAging is a phenomenon that all living organisms surely face. d-galactose (D-gal) has been used to develop an aging model of brain. Lithium (Li) has been proposed to have neuroprotective properties in relation to several neurological disorders. The goal of the current studyis to evaluate the effect of Lithium Chloride (LiCl) on D-gal induced neurological disorders and oxidative stress.MethodsRats were treated with D-gal at a dose of 300 mg/ml/kg and various doses of LiCl (20, 40 and 80 mg/ml/kg) for 14 days. After that behavioral analysis (Elevated plus maze (EPM); Light dark box test (LDT); Morris water maze (MWM); Forced swim test (FST)) were performed. Animals were decapitated after behavioral tests and brain samples were collected for biochemical (malondialdehyde (MDA); superoxide dismutase (SOD); catalase (CAT); glutathione peroxidase (GPx); acetylcholiesterase (AChE)) and neurochemical analysis (5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA)).ResultsThe results showed that administration of LiCl at all doses ameliorates D-gal induced, decreased time spent in the open arm and light box in EPM and LDT respectively, increased immobility in FST, increased latency escape in MWM, increased MDA levels, decreased antioxidant enzyme, increased AChE activity and decreased 5-HT metabolism.ConclusionsIn conclusion, the present study indicated that D-gal induced anxiety/depression like symptoms and memory impairment were ameliorated by LiCl (at all doses) possibly via its antioxidant effects and normalizing 5-HT function.     

川芎嗪对阿尔采末病模型小鼠学习记忆能力的影响及其机制初探

目的观察川芎嗪(tetramethylpyrazine,TMP)对AD模型小鼠学习记忆能力的改善作用及其机制。方法采用D-gal与NaNO2联合腹腔注射和AlCl3灌胃两种造模方法建立AD模型小鼠,灌胃给予TMP(100mg.kg-1)观察疗效,检测各组小鼠的逃避潜伏期、脑组织AChE、SOD活性、MDA含量及大脑皮层Aβ、NF-κB表达的变化。结果TMP可使D-gal与NaNO2联合诱导的AD模型鼠与AlCl3诱导的AD模型鼠的逃避潜伏期缩短(P<0.05);②TMP可使D-gal与NaNO2联合诱导的AD模型鼠与AlCl3诱导的AD模型鼠脑组织中,AChE活性分别降低16%和19%;使SOD活性分别提高50%和39%;使MDA含量分别降低27%和34%;上述检测结果与对照组比较差异均有显著性(P<0.05);③TMP可明显降低两种AD模型鼠脑组织中Aβ、NF-κB的表达(P<0.05)。结论TMP可改善化学诱导的AD模型小鼠学习记忆能力障碍,可能与提高SOD活性、降低MDA含量、降低AChE活性、降低脑组织中Aβ、NF-κB的表达等有关。     

当归芍药散二氯甲烷提取部位对D-半乳糖致衰老小鼠学习记忆能力的影响

目的研究当归芍药散二氯甲烷提取部位(DSP)对D-半乳糖(D-gal)致小鼠学习记忆能力障碍及神经毒性的改善作用。方法 ICR小鼠随机分为空白组,模型组,维生素E组,当归芍药散二氯甲烷提取部位低、高剂量组。空白组以外各组皮下注射D-半乳糖(50mg.kg-1.d-1)50d制备小鼠亚急性衰老模型。用跳台法和Morris水迷宫法评价小鼠的学习记忆能力,测定小鼠血清中总超氧化物歧化酶(T-SOD)、丙二醛(MDA)、谷胱甘肽过氧化酶(GSH-Px)活性和脑组织匀浆中谷胱甘肽/氧化型谷胱甘肽(GSH/GSSG)比值、Na+-K+-ATPase活性和淀粉样蛋白β(Aβ)含量。结果当归芍药散二氯甲烷提取部位能够显著提高衰老小鼠的学习记忆能力(P<0.05或P<0.01),提高衰老模型小鼠血清SOD、GSH-Px及脑组织Na+-K+-ATP酶活性,并升高GSH/GSSG比值,减少血清MDA(P<0.05或P<0.01);减少脑内Aβ含量(P<0.05)。结论当归芍药散二氯甲烷提取部位能够改善D-半乳糖衰老模型小鼠的学习记忆障碍,其作用可能与提高脑组织的抗氧化能力、降低中枢神经毒性有关。