Effect of Yizhitongxuan decoction on learning and memory ability,Gαq/11 expression and Na~＋-K~＋-ATP enzyme activity in rat models of Alzheimer＇s Disease

OBJECTIVE： To study the effects of Yizhitongxuan decoction on learning and memory abilities, Gαq/11expression and Na＋-K＋-ATPenzymeactivityin rat models of Alzheimer＇s disease（AD） caused by injecting Aβ25-35 into the hippocampus.METHODS： Ninety male Wistar rats（age ≥10 months）were selected and injected with Aβ25-35 into their hippocampi to establish model animals,which were randomly divided into six groups including a sham-operated group（blank group）, a model group, a donepezil HCL group（Western Medicinegroup）,and ahigh/general/dilute concentrations of Yizhitongxuan decoction groups（TCMⅠⅡⅢgroup）.The Morris watermaze was used to examine the learning and memory abilities of rats in each group by place navigation and spatial probe tests.Then, the rats were sacrificed to collect the hippocampi for biochemical tests, using western blotting to detect the expression of Gαq/11 and an ultramicro Na＋-K＋-ATP enzyme kit to measure Na＋-K＋-ATP enzyme activity.RESULTS：Yizhitongxuan decoction improved model rats＇ learning and memory abilities, and increased the expression of Gαq/11 in the hippocampus and the level of Na＋-K＋-ATP enzyme activity in braintissue.CONCLUSION： Yizhitongxuan decoction could improve model rats＇ learning and memory abilities,and had a regulating effect on the expression of Gαq/11and Na＋-K＋-ATP enzyme activity.     

Shen-Zhi-Ling oral solution improves learning and memory ability in Alzheimer's disease mouse model

OBJECTIVE: To investigate the effector mechanisms and effector targets of Shen-Zhi-Ling(SZL)oral solution in the treatment of Alzheimer's disease(AD).METHODS: In this study, we carried out gavage with SZL oral solution in an APP/PS-1 heterozygous double transgenic AD mouse model for 12 continuous weeks.Haematoxylin and eosin staining, Nissl staining and Annexin V/Propidium Iodide staining were used to detect the brain histopathology in AD mouse model.Immunofluorescence staining was used to detect the expression levels of autophagy's proteins.Morris water maze test was used to detect the learning and memory ability in AD mouse model.RESULTS: Pathological results showed that neuronal loss in the hippocampus of mice in the SZL intervention group was significantly alleviated and the number of apoptotic neurons was significantly decreased compared with the control group(physiological saline and non-intervention groups).Immunofluorescence staining results showed that the expression of autophagy activators, Beclin-1 and LC3 B, was significantly increased in the hippocampal neurons of mice of the SZL intervention group,while the expression of the apoptotic factor, caspase-3, was significantly decreased.At the same time, hippocampal accumulation of Aβ42 protein was significantly decreased.In addition, results of the water maze experiment showed that the latency period in mice from the SZL intervention group was significantly reduced.CONCLUSION: In summary, we believe that the SZL oral solution significantly activates autophagy in hippocampal neurons, effectively reducing the accumulation of Aβ42 peptides, alleviating neuronal injury and apoptosis, and ultimately improving the cognitive function in a mouse model of AD.     

THE ANTI-DEPRESSIVE MECHANISM OF ELECTROACUPUNCTURE ON THE EXPRESSION OF BRAIN-DERIVED NEUROTROPHIC FACTOR

Objective: Electroacupuncture(EA) has been reported to be effective for treating depression.The purpose of this study was to explore the mechanism of EA's function on the expression of brain-derived neurotrophic factor(BDNF), which is known to be associated with depressive disorders.Methods: A rat model of depression induced by chronic stress was established by alternating the following methods, water-break(24 h), night light(12 h), swimming(4 ℃, 5 min), shaking(30 min) and bounding(3 h), every day for four weeks.Rats were randomly divided into six groups(n=10 each): normal, normal+hand acupuncture, model, model+acupuncture, model+hand acupuncture, and model+paroxetine.EA was given at acupoints Baihui(GV20), Yintang(GV29) and Neiguan(PC6) for 10 min(2/100 Hz alternating, 0.2 mA) every other day for four weeks.The rats were decapitated and the brain tissues were collected after four weeks of treatment.Westernblot method was used to test BDNF in hippocampus and prefrontal cortex.Results: Compared to the normal group, protein expression of BDNF significantly decreased in the model group(P0.01) in the hippocampus and prefrontal cortex.In the hippocampus: compared with the model group, the hand acupu ncture group andthe EA group obviously increased(P0.01), and the paroxitine group increased(P0.05); In the prefrontal cortex: compared with the model group, the hand acupuncture group, the EA group and the paroxitine group obviously increased(P0.01).BDNF expression increased in the model+hand acupuncture group and the model+paroxitine group compared with the model group(P0.01) and in the model+hand acupuncture group compared with the mode+EA group(P0.01).Conclusion: Solitary combined with chronic stress can significantly reduce the expression of BDNF.Hand acupuncture, EA and paroxetine intervention can improve the expression level of BDNF.Acupuncture treatment has obvious advantages in raising BDNF protein expression level.These indicated that acupuncture can alleviate depression through stimulating the Ras-MAPK-ERK pathway and expanding protein expression of BDNF to protect the neurons.     

Protection of Effective Component Group from Xiaoshuan Tongluo on Brain Injury after Chronic Hypoperfusion in Rats

Objective To investigate the protective effects of purified effective component group in extract from Xiaoshuan Tongluo(CGXT) formula on chronic brain ischemia in rats.Methods CGXT 75,150,and 300 mg/kg or vehicle were ig administered daily for four weeks to rats with bilateral common carotid arteries ligation(BCCAL) .From the day 24 to 28 after BCCAL,Morris water maze was performed to assess the learning and memory impairment of rats.Four weeks after BCCAL,brain gray and white matter damage were assessed.Results In Morris test,the mean escape latency of rats in the CGXT(150 and 300 mg/kg) groups was significantly shorter than that in the vehicle group.CGXT also attenuated the neuronal damage in hippocampus and cortex and reduced the pathological damage in the optic tract and corpus callosum.Conclusion CGXT could improve learning and memory impairment resulted from BCCAL in rats.These results provide the experimental basis for the clinical use of CGXT in stroke treatment and may help in investigation of multimodal therapy strategies in ischemic cerebrovascular diseases including stroke.     

Antidepressant-like effect of essential oil of Perilla frutescens in a chronic,unpredictable, mild stress-induced depression model mice

Perilla frutescens（Perilla leaf）, a garnishing vegetable in East Asian countries, as well as a plant-based medicine, has been used for centuries to treat various conditions, including depression. Several studies have demonstrated that the essential oil of P. frutescens（EOPF） attenuated the depressive-like behavior in mice. The present study was designed to test the anti-depressant effects of EOPF and the possible mechanisms in an chronic, unpredictable, mild stress（CUMS）-induced mouse model. With the exposure to stressor once daily for five consecutive weeks, EOPF（3, 6, and 9 mg·kg-1） and a positive control drug fluoxetine（20 mg·kg-1） were administered through gastric intubation to mice once daily for three consecutive weeks from the 3rd week. Open-field test, sucrose consumption test, tail suspension test（TST）, and forced swimming test（FST） were used to evaluate the behavioral activity. The contents of 5-hydroxytryptamine（5-HT） and its metabolite, 5-hydroxyindoleacetic acid（5-HIAA）, in mouse hippocampus were determined by HPLC–ECD. Serum interleukin（IL）-1, IL-6, and tumor necrosis factor（TNF）-α levels were evaluated by enzyme-linked immunosorbent assay（ELISA）. The results showed that CUMS significantly decreased the levels of 5-HT and 5-HIAA in the hippocampus, with an increase in plasma IL-6, IL-1β, and TNF-α levels. CUMS also reduced open-field activity, sucrose consumption, as well as increased immobility duration in FST and TST. EOPF administration could effectively reverse the alterations in the concentrations of 5-HT and 5-HIAA; reduce the IL-6, IL-1β, and TNF-α levels. Moreover, EOPF could effectively reverse alterations in immobility duration, sucrose consumption, and open-field activity. However, the effect was not dose-dependent. In conclusion, EOPF administration exhibited significant antidepressant-like effects in mice with CUMS-induced depression. The antidepressant activity of EOPF might be related to the relation between alteration of seroto     

Ameliorating effects of constituents from Cortex Acanthopanacis Radicis on memory impairment in mice induced by scopolamine

OBJECTIVE：To investigate the effects of active con- stituents extracted from Cortex Acanthopanacis Radicison improving the impaired memory in mice models. METHODS： The mice models of memory impair- ment were established using scopolamine. Amelio- rating effects of the fractions and constituents on scopolamine-induced memory impairment in vivo were investigated using passive avoidance and Morris water-maze task tests, and their anti-acetyl- cholinesterase（AChE） and antioxidant activities in vitro examined. The isolation of constituents was performed by chromatographic methods and their structures were identified on the basis of instru- mental analysis. RESULTS： Among the fractions tested, ethylacetate fraction exhibited the anti-AChE activity（25.83%± 0.23%） properly and excellent 2,2-diphenyl-1-picryl- hydrazyl（DPPH） radical and superoxide anion scav- enging capacity（87.50% ± 0.83% and 60.22% ± 0.43%, respectively）. However, the methylene chlo- ride fraction was much more active than the ethyl- acetate fraction in the passive avoidance task test（167.5% increase of step-through latency time） and Morris water-maze task test（33.3% decrease of es-cape latency time）. Four constituents, β-sitosterol, stigmasterol, sesamin, and hyperin were isolated from the methylene chloride fraction, among them, hyperin showed anti-acetylcholinesterase and anti-oxidant activities remarkably. Moreover, hyperin exerted a potent effect（146±38） s on mem- ory improvement in terms of passive avoidance task test compared with the reference compound tacrine（162±43） s at a dose of 2.5 mg/kg. CONCLUSION： Hyperin, a flavonoid glucoside iso- lated from Cortex Acanthopanacis Radicis, inhibited AChE activity and potently ameliorated scopol- amine-induced memory impairment, and its action may be partially mediated by the acetylcholine-en- hancing cholinergic nervous system.     

EFFECT OF ELECTROACUPUNCTURE ON THE BEHAVIOR AND THE EXPRESSION OF Aβ, AND LRP1 IN HIPPOCAMPAL MICROVESSELS OF APP695V717I TRANSGENIC MICE

Objective: To investigate the effects of electroacupuncture(EA)therapy on the expression of amyloid β protein(Aβ) and LDL receptor-related protein 1(LRP1) in the hippocampal microvessels,which may be part of the mechanisms of EA therapy on Alzheimer's disease(AD).Methods: APP695V717 I transgenic mice were randomly divided into model group and EA group; C57BL/6 mice were used as the control group.After 3 months of treatment by EA therapy at DU20 and KI1(15 min per other day, 2/100 Hz, 1-2 mA), the learning and memory behavior of mice was measured by Lashley Ⅲ water maze test and the expression level of Aβ, and LRP1 in the hippocampal microvessels were measured by immunohistochemical method.Results: The learning and memory capacity and the expression level of LRP1 in the model group were lower than those in the control group(P0.01); and the expression level of Aβ was significantly higher(P0.01).The learning and memory capacity and the expression level of LRP1 in the EA group were higher and the expression level of Aβ was significantly lower than those in the model group(P0.05).Conclusion: EA can improve the learning and memory capacity of the APP transgenic model by increasing the capacity of LRP1 and lowering the Aβ deposition in cerebral microvessels.     

Anti-inflammation of Tripterygium wilfordii Polycoride on Macrophages and Its Regulation to Inflammation via TLR4/NF-κB

Objective To investigate the inhibitory effect of Tripterygium wilfordii polycoride(TWP) towards the pro-inflammatory factors(TNF-α and IL-1β) on the inflammatory reaction in macrophages induced by LPS and its regulatory effect and influence on the inflammation via TLR4/NF-k B. Methods The MTT method was adopted to test the effect of drugs, TWP, dexamethasone(DXM) and azathioprine(AZA) on cell growth and to select the appropriate concentration. LPS was used to induce the inflammatory reaction in RAW264.7 cell line of mice. Elisa kit was adopted to test the levels of TNF-α and IL-1β. Western blotting was adopted to test the protein expression of TNF-α and IL-1β. RT-PCR was adopted to test the expression of TLR4 and NF-κB. Results The inhibiting effect of TWP on the release of TNF-α and IL-1β in a dose dependent manner. The inhibitory effect of three different TWP dose groups is weaker than that in DXM group. However, TWP in high dose is better than AZA on TNF-α and is as strong as AZA on IL-1β. The dose dependent manner also exits in the effect on the expression of TLR4 and NF-κB, the effect is not weaker, but even stronger than that of DXM and AZA. Conclusion The research shows that down regulation of TLR4 and NF-k B p65 may be one of the mechanisms about the TWP inhibitory effect on TNF-α and IL-1β.     

Long-term consumption of virgin coconut (Cocos nucifera) oil diet impairs learning and memory in CD1 mice

Objective: Virgin coconut oil (VCO) has been used in the management of dementia in Alzheimer’s disease (AD). Therefore, this research investigated the effect of long-term consumption of VCO diet on learning and memory in CD1 mice. Methods: Thirty male CD1 mice (divided into three groups, n = 10) were fed with standard rodent chow (control), 5% and 20% VCO diets (respectively) for 28 d. The Morris Water Maze (MWM) test was used to test the effect of VCO on visuo-spatial learning and memory, while the Novel Object Recognition Test (NORT) was used to measure short- and long-term recognition memory. Results: Learning performance of mice did not differ in the MWM. During the probe trial, duration in the retention quadrant and annulus crossings were lower (P < 0.05) in the 5% and 20% VCO diet groups compared to the control diet group, showing that VCO impaired visuo-spatial memory. During the NORT, mice showed more total approaches in the 20% VCO diet group (P < 0.05) compared to control and the 5% VCO diet groups during the short-term memory test. During the long-term memory retention test, the total approaches were also higher in the 20% VCO group compared to control and 5% VCO group (P > 0.05). The discrimination index was also lower in the 20% VCO group compared to control and 5% VCO diet groups indicating impaired long-term cognitive memory in mice given 20% VCO diet. Histological examination of brains showed damage within the CA1 pyramidal cell layer of the hippocampus in the 20% VCO diet group, in line with the behavioural observations. Conclusion: Long-term consumption of virgin coconut oil diet impairs memory in mice.     

山茱萸多糖对衰老模型大鼠学习记忆能力及海马突触可塑性的影响

目的:观察山茱萸多糖对衰老模型大鼠学习记忆能力、海马脑源性神经生长因子(BDNF),酪氨酸蛋白激酶B(Trk B)蛋白表达及海马长时程增强(LTP)的影响,并探讨其机制。方法:清洁级SD大鼠40只,随机数字表法分为正常组、模型组、山茱萸多糖低、高剂量组,每组10只,采用D-半乳糖(140 mg·kg~(-1)·d-1)皮下注射构建大鼠衰老模型,同时正常组、模型组每天给予生理盐水、低剂量组和高剂量组给予山茱萸多糖(0.14,0.28 g·kg~(-1)·d-1)灌胃6周。Morris水迷宫检测学习记忆能力,高频刺激海马CA3区Schaffer侧支,在同侧海马CA1区诱导LTP的方法检测大鼠海马神经元突触可塑性的变化,免疫组化法检测海马神经元BDNF和Trk B蛋白的表达情况。结果:与正常组比较,模型组平均逃避潜伏期明显延长,在目标象限内游泳的距离占总距离的百分比和探索次数明显减少,海马LTP幅度显著降低,海马BDNF和Trk B蛋白表达降低(P0.01)。高剂量组与模型组比较平均逃避潜伏期明显降低,在目标象限内游泳的距离占总距离的百分比和探索次数明显升高,海马LTP幅度显著升高,海马BDNF和Trk B蛋白表达升高(P0.01)。结论:山茱萸多糖可通过提高海马BDNF和Trk B的表达及大鼠海马CA1区的LTP,明显改善突触的可塑性,这可能是山茱萸多糖提高学习记忆能力的重要机制之一。     

“补肾活血”针刺法对老年性痴呆模型SAMP8小鼠学习记忆能力和脑组织AChE活性的影响

目的观察“补肾活血”针刺法对老年痴呆模型SAMP8小鼠学习记忆能力和脑组织AChE活性的影响。方法选取8月龄SAMP8小鼠20只,随机分为针刺组10只,SAMP8空白对照组10只,另选取10只8月龄的SAMR1小鼠为SAMR1对照组。疗程结束后评定疗效,测各组小鼠的学习记忆能力及脑组织中AchE含量。结果与SAMR1组比较,SAMP8空白对照组小鼠在隐蔽平台试验中表现出明显的学习记忆障碍,逃避潜伏期显著延长（P〈0．05）,针刺组逃避潜伏期较SAMP8空白对照组显著缩短（P〈0．05）;探索试验巾针刺组原平台象限的停留时间和穿越原平台次数明显多于SAMP8空白对照组（P〈0．05）,与SAMR1对照组比较差异无统计学意义（P〉0．05）;针刺组针刺后脑组织AChE活性较SAMP8空白对照组显著性降低（P〈0．05）,与SAMR1对照组比较差异无统计学差异（P〉0．05）。结论“补肾活血”针刺法能有效提高AD小鼠学习记忆能力,这种作用可能是通过抑制脑组织AChE活性实现的。     

山楂叶总黄酮对血管性痴呆大鼠学习记忆及海马AChE, ChAT活性的影响

目的:探讨山楂叶总黄酮(total flavone of Hawthorn leaf,TFHL)对血管性痴呆大鼠空间学习记忆障碍的治疗作用及机制。方法:健康雄性SD大鼠64只,随机分为假手术组(sham control group)、模型组(model group)、TFHL 70,140 mg·kg-1及银杏叶片组(3.5 mg·kg-1),每组16只。采用永久性双侧颈总动脉结扎法制备血管性痴呆大鼠模型,TFHL 70,140 mg·kg-1组连续给药36 d。采用Morris水迷宫评价大鼠的空间学习学习记忆能力,分光光度比色法检测大鼠海马乙酰胆碱酯酶(AChE)和乙酰胆碱转移酶(ChAT)活性。结果:与假手术组比较,血管性痴呆模型组大鼠学习记忆能力显著降低,大鼠逃避潜伏期明显延长(P<0.05),穿越平台区次数显著减少(P<0.05),平台象限游泳距离百分比显著降低(P<0.05);ChAT活性明显降低(P<0.05),AChE活性显著增强(P<0.05)。TFHL及银杏叶片能改善血管性痴呆大鼠学习记忆能力,缩短大鼠逃避潜伏期(P<0.05),增加大鼠穿越平台次数及平台象限游泳距离百分比(P<0.05),增强ChAT活性(P<0.05),降低AChE活性(P<0.05)。结论:TFHL可通过提高海马ChAT活性、降低AChE活性改善血管性痴呆大鼠海马胆碱能神经系统的功能,从而改善血管性痴呆大鼠的学习记忆功能。     

ACUPUNCTURE STIMULATION IMPROVES MEMORY IMPAIRMENT INDUCED BY SCOPOLAMINE IN RATS

Objective: The purpose of this study was to examine whether acupuncture stimulation at the Baihui(GV20) improves memory defects caused by administration of scopolamine(SCO) to the rats.The effects of acupuncture stimulation at the GV20 on the cholinergic system as well as the expression of brain-derived neurotrophic factor(BDNF) and cAMP-response element-binding protein(CREB) in the hippocampus were also investigated.Methods: Male rats were administered with SCO(2 mg/kg, i.p.) once daily for 14 days.Acupuncture stimulation at GV20 was performed for 5 min before SCO injection.Results: Acupuncture stimulation at GV20 improved memory impairment as measured by the passive avoidance test(PAT) and reduced the escape latency for finding the platform in the Morris water maze(MWM) test.Acupuncture stimulation at the GV20 significantly alleviated memory-associated decreases in the expression levels of choline acetyltransferase(ChAT), BDNF and CREB proteins in the hippocampus.Additionally, acupuncture stimulation at the GV20 significantly restored the expression of choline transporter 1(CHT1), vesicular acetylcholine transporter(VAChT), BDNF and CREB mRNAs in the hippocampus.Conclusion: These results demonstrated that acupuncture stimulation at the GV20 has significant neuroprotective effects against neuronal impairment and memory dysfunction caused by SCO in rats.Thus, these findings suggested that acupuncture stimulation at the GV20 might be a useful therapy in various neurodegenerative diseases for the improvement of cognitive functioning via stimulating cholinergic enzyme activities and regulating BDNF and CREB expression in the brain.     

熟地黄有效成分5-HMF对皮质酮损伤型海马神经元GCR、BDNF、SGK表达的影响

目的:观察熟地黄中有效成分5-羟甲基糠醛(5-HMF)对高浓度皮质酮(CORT)致海马神经元损伤及学习记忆相关蛋白学习记忆相关蛋白(GCR)、脑源性神经营养因子(BDNF)、血清和糖皮质激素调节蛋白激酶(SGK)蛋白表达的影响。方法:用24h新生大鼠原代培养海马神经细胞。第8天细胞用药处理,将细胞分为3组:正常对照组、模型组及5-HMF组。24h后,通过MTT法测定细胞活性,生化方法检测衰老特异性指标β-半乳糖苷酶活性,Western Blot检测学习记忆相关蛋白GCR、BDNF、SGK的基因表达。结果:与正常组相比,模型组细胞活力显著下降,β-半乳糖苷酶活性显著升高,GCR、BDNF、SGK蛋白表达显著性降低;0.5mg/L的5-HMF明显提高细胞活力,降低β-半乳糖苷酶活性,提高模型细胞GCR、BDNF、SGK基因表达(P0.05,P0.01)。结论:0.5mg/L 5-HMF可以保护大鼠海马神经细胞免遭高浓度皮质酮的损伤,通过调节GCR、BDNF、SGK的基因表达,可能在延缓学习记忆功能退化中发挥作用。     

铁筷子挥发油对慢性脑缺血致血管性认知功能障碍大鼠的作用及机制研究

目的 探究苗药铁筷子[腊梅Chimonanthus praecox及山腊梅C. nitens的干燥根]挥发油对慢性脑缺血（chronic cerebral hypoperfusion,CCH）致血管性认知功能障碍（vascular cognitive impairment,VCI）大鼠的作用及机制。方法 采用改良的双侧颈总动脉结扎（bilateral common carotid artery occlusion,BCCAO）法建立CCH模型,将造模成功大鼠随机分为模型组及铁筷子挥发油高、中、低剂量（80、40、20 mg/kg）组和丁苯酞（63 mg/kg）组,另设假手术组,给予相应药物干预28 d,采用水迷宫实验检测各组大鼠学习记忆能力;采用旷场实验、Y迷宫实验检测各组大鼠自主活动性和新奇事物探索能力;采用苏木素-伊红（HE）染色、Nissl染色、TUNEL染色观察各组大鼠大脑皮层及海马CA1区神经细胞结构变化、尼氏小体以及凋亡细胞数量变化;采用ELISA法检测各组大鼠血清中脑源性神经营养因子（brain-derived neurotrophic factor,BDNF）水平;采用比色法检测各组大鼠海马组织中乙酰胆碱酯酶（acetylcholinesterase,AChE）和乙酰胆碱转移酶（cholineacetyltransferase,ChAT）的活性;采用Western blotting法检测各组大鼠海马组织中BDNF、酪氨酸激酶受体B（tyrosine kinase receptor B,TrkB）、磷酸化TrkB（phosphorylated TrkB,p-TrkB）、磷脂酰肌醇-3-激酶（phosphatidylin-ositol-3-kinase,PI3K）、蛋白激酶B（Akt）、p-Akt和半胱氨酸天冬氨酸蛋白酶-3（cystein-asparate protease-3,Caspase-3）蛋白表达。结果 与模型组比较,铁筷子挥发油组大鼠逃避潜伏期缩短（P＜0.05、0.01）,穿越平台次数和跨格次数提高（P＜0.05、0.01）,在新异臂所待时间延长（P＜0.05）;神经细胞结构的变性得到改善,脑组织中尼氏小体的数量提高（P＜0.05）,细胞凋亡减少（P＜0.05）;血清中BDNF水平及海马组织中ChAT活性升高（P＜0.05、0.01）,海马组织中AChE活性降低（P＜0.05）;海马组织中BDNF、TrkB、p-TrkB、PI3K和p-Akt蛋白表达水平均显著升高（P＜0.05、0.01）,Caspase-3蛋白表达水平降低（P＜0.05）。结论 苗药铁筷子挥发油可以改善CCH致VCI大鼠认知功能障碍,其作用机制可能与激活BDNF/TrkB/PI3K/Akt信号通路有关。     

补阴益智汤配方颗粒对东莨菪碱所致小鼠学习记忆损伤的保护作用

目的:考察给予东莨菪碱造模后,补阴益智汤配方颗粒对小鼠学习记忆损伤的保护作用,并通过神经递质和突触可塑性相关蛋白考察其可能的机制。方法:雄性昆明种小鼠50只,通过腹腔注射东莨菪碱(3.0 mg·kg~(-1))建立小鼠学习记忆损伤模型。随机分为正常组、模型组和补阴益智汤高、中、低(18,6,2 g·kg~(-1)),造模后,连续给药2周,通过小鼠跳台实验,Morris水迷宫实验和新物体辨别实验,考察小鼠学习记忆的能力。采用高效液相色谱法测定小鼠前额叶皮层和海马内氨基酸类神经递质的水平,通过蛋白质免疫印迹法(Western blot)检测小鼠海马区内突触核蛋白(Syn),突触后密度蛋白-95(PSD-95)和脑源性神经营养因子(BDNF)蛋白的表达。结果:与正常组比较,模型组小鼠跳台实验、水迷宫实验潜伏期显著缩短(P0.01),触电次数显著增加(P0.01),对新物体的探索时间显著缩短(P0.01),海马及前额叶皮层内γ-氨基丁酸(GABA)含量增多,而谷氨酸(Glu)含量均显著降低(P0.01),海马内Syn,PSD-95和BDNF蛋白表达量均明显增多(P0.05,P0.01);与模型组比较,中、高剂量给药组潜伏期明显延长(P0.05,P0.01),其中高剂量组触电次数明显减少(P0.05);对新物体的探索时间显著延长(P0.01),GABA含量明显降低(P0.05,P0.01),Glu含量以及Syn,PSD-95和BDNF蛋白表达量明显升高(P0.05,P0.01)。结论:补阴益智汤配方颗粒可以改善东莨菪碱所致的小鼠学习记忆损伤,其机制可能与改变海马及前额叶皮层内Glu/GABA以及调节小鼠海马脑区内Syn和PSD-95蛋白的表达有关。     

补骨脂汤对痴呆大鼠海马NR2B、BDNF/TrkB表达的影响

目的 为探讨补骨脂汤对改善血管性痴呆大鼠的空间学习记忆的机理.方法 用双侧结扎颈动脉反复灌注,用Morris试验测试大鼠的空间学习记忆,RT-PCR测定与学习记忆密切相关的NR2B、BDNF/TrkB基因表达产物.结果 补骨脂汤高、低剂量组的逃避潜伏期都明显短于模型组(P<0.01),补骨脂汤高、低剂量,均可明显提高NR2B、BDNF/TrkBmRNA表达(P<0.05).结论 补骨脂汤能明显改善血管性痴呆大鼠的空间记忆,其可能的机制是通过提高NR2B、BDNF/TrkBmRNA表达水平而发挥作用的.     

增忆方对亚急性衰老大鼠记忆及海马NO/NOS的影响

目的:探讨增忆方对亚急性衰老大鼠空间学习记忆能力的作用以及对海马一氧化氮及一氧化氮合酶的影响。方法:迷宫观察动物的空间记忆能力,同时检测海马一氧化氮(NO)含量和一氧化氮合酶(NOS)活性。结果:模型组大鼠逃避潜伏期显著延长(P<0.01),海马NO含量和NOS活性显著降低(P<0.01);增忆方能显著缩短模型大鼠的逃避潜伏期,升高海马NO水平和NOS活性(P<0.05)。结论:增忆方有提高亚急性衰老大鼠空间学习能力作用,其作用机制可能是通过影响海马内NO/NOS水平有关。     

地黄饮子对慢性脑低灌注大鼠学习记忆及海马AChE,ChAT的影响

目的:探讨地黄饮子对慢性脑低灌注大鼠学习记忆及海马乙酰胆碱酯酶(AChE)、乙酰胆碱转移酶(ChAT)的影响。方法:采用双侧颈总动脉结扎制作大鼠慢性脑缺血模型,通过Morris水迷宫试验测定地黄饮子对慢性脑低灌注大鼠学习记忆功能改善情况,并测定大鼠海马脑组织AChE,ChAT的含量。结果:地黄饮子组(10,20 g.kg-1)与模型对照组比较,Morris水迷宫试验逃避潜伏期缩短,跨越平台次数增加,海马AChE和ChAT含量显著升高(P<0.05)。结论:地黄饮子能改善慢性脑低灌注大鼠学习记忆功能,可能与保护胆碱能系统有关。