Kongsheng Zhenzhong pill's effect on the learning and memory ability and its neuroprotective effects in vascular dementia rats

Clinical reports have demonstrated that the Kongsheng Zhenzhong pill （KSZZP）, a classical prescription deriving from Valuable Prescription for Emergencies, has good therapeutic effects on vascular dementia. However, the mechanisms that mediate its effects remain unclear. In this study, the expression of N-methyI-D-aspartate receptor 1 mRNA, the content of nitric oxide, and the concentration of calcium in neurons was determined with in situ hybridization, spectrophotometry and flow cytometry, respectively. In addition, the expressions of N-methyI-D-aspartate receptor 1, nerve growth factor protein, and glial cell line-derived neurotrophic factor protein were detected with immunohistochemistry. We found that KSZZP could significantly decrease the expression of N-methyI-D-aspartate receptor 1 mRNA and protein, the content of nitric oxide, and the concentration of calcium in neurons. KSZZP also increased the expression of nerve growth factor and glial cell line-derived neurotrophic factor protein in the hippocampus CA1 region and in the cerebral cortex. Morris water maze and passive avoidance tests verified that KSZZP ameliorated the cognitive impairments of vascular dementia rats. Moreover, the KSZZP-induced improvements in the cognitive functions of vascular dementia rats were correlated with both inhibition of N-methyl-D-aspartate-induced excitable neurotoxicity and elevation of neurotrophic factor expression.

Electropuncture influences on learning, memory, and neuropeptide expression in a rat model of vascular dementia

BACKGROUND： Studies in recent years have indicated that several neuropeptide-like substances, such as arginine vasopressin （AVP）, somatostatin （SS）, and β-endorphine （β-EP）, are involved in the process of cerebral ischemic damage to cranial nerves. OBJECTIVE： To observe the effects of electropuncture on back-shu points, as well as the influence on learning and memory, AVP, SS, and β-EP levels in plasma and brain were measured in a rat model of vascular dementia （VD）. DESIGN： Randomized controlled trial. SETTING： College of Acupuncture and Massage of Guangzhou University of Chinese Medicine. MATERIALS： This experiment was performed at the Animal Experiment Center of Guangzhou University of TCM from December 2005 to December 2006. A total of 48 healthy adult male Sprague Dawley rats of SPF-grade, 180-220 g, were provided by The Animal Experiment Center of Guangzhou University of Traditional Chinese Medicine. The following instruments were used： SDQ-30 Dipolar Radio-frequency Electrocoagulator （Shanghai Operation Instrument Factory）, Morris Water Maze （The Animal Experiment Center of Guangzhou University of Traditional Chinese Medicine）, Type G6805-1 Treating Equipment （Huasheng Equipment Factory, Qingdao, China）. METHODS： ① Eight rats were randomly selected for the control group; the remaining 40 rats underwent 4-vascular occlusion to establish a cerebral ischemia model. Due to the death of 13 rats and 2 hemiplegies during model establishment, there was a total of 25 model rats available for testing. The model rats were divided randomly into 3 groups according to their body weight： electropuncture group （n = 9）, medication group （n = 8）, and VD group （n = 8）. ② Electropuncture group： 25 mm needles （28 gauge） were used to electropuncture （150 Hz, continuous waves, 1.0-2.0 mA, duration of 20 minutes） the following acupoints： Baihui （GV20）, Geshu （BLIT）, Pishu （BL20）, and Shenshu （BL23）. The acupoints were located according to Experimental acupuncturology and were stimulated electrically by G6805-1 treating equipment. Medication group： Nimotop （certificate number： 110156; 0.6 mg/mL suspension）, 20 mL/kg, was perfused once daily intragastrically for 15 days. Model group： the rats were fed once daily with 150 g/L isotonic NaCl for 15 days （20 mL/kg）. MAIN OUTCOME MEASURES： Morris water maze testing was employed to study learning and memory behavior. Levels of AVP, SS, and β -EP were measured in plasma and brain radioimmunoassay （RIA）. RESULTS： A total of 33 Sprague Dawley rats were included in the final analysis. In the VD group, AVP and SS levels in plasma and brain were lower than the other groups （P 〈 0.01）. However, β-EP plasma levels decreased significantly （P 〈 0.01）, while β-EP brain levels increased significantly （P 〈 0.01）. The AVP and SS content in plasma and brain, as well as β -EP in plasma, increased （P 〈 0.01）. The levels of β-EP in the brain decreased （P 〈 0.01）. Morris Water maze results demonstrated that the electropuncture, medication, and control groups had shorter escape times than the VD group （P 〈 0.01）. Animals in the electropuncture, medication, and control groups spent more time in the platform quadrant than in the other three quadrants （P 〈 0.01 ）. CONCLUSION： Electropuncture can regulate the amount of AVP, SS, and β-EP in the plasma and brain, and correlates with improved learning and memory in a rat model of VD.

Tongqiao Huoxue Decoction ameliorates learning and memory defects in rats with vascular dementia by up-regulating the Ca^(2+)-CaMKII-CREB pathway

The present study was aimed at determining the effects of Tongqiao Huoxue Decoction （TQHXD） on the Ca2＋-CaMKII-CREB pathway and the memory and learning capacities of rats with vascular dementia （VD）. The rat VD model was established by using an improved bilateral carotid artery ligation method. The Morris water maze experiment was used to evaluate the ethology of the VD rats following treatments with TQHXD at 3.01, 6.02, and 12.04 g.kg-1 per day for 31 days. At the end of experiment, the hippocampus were harvested and analyzed. Western blotting and RT-PCR were used to measure the expression levels of calmodulin-binding protein kinase II（CaMKII）, protein kinase A（PKA）, cAMP-response element binding protein（CREB）, and three N-methyl-D-aspart^c acid receptor subunits （NR1, NR2A, and NR2B）. Our results revealed that TQHXD could alleviate the loss of learning abilities and increase the memory capacity （P 〈 0.05 and P 〈 0.01 vs the model group, respectively）. The treatment with 6.02 and 12.04 g.kg-1 of TQHXD significantly up-regulated the Ca2＋-CaMKII-CREB pathway in the hippocampus. In conclusion, TQHXD showed therapeutic effects on a bilateral carotid artery ligation-induced vascular dementia model, through the up-regulation of calcium signalling oathwavs.

Effect of Electroacupuncture on Learning and Memory in Rats with Vascular Dementia

Objective：To observe the effect of electroacupuncture on learning and memory in rats with vascular dementia.Methods：Seventy-two SD rats were randomly divided into 4 groups,a normal group,a sham operation group,a model group and an electroacupuncture （EA） pretreatment group.Modified intraluminal embolism method with nylon thread was applied to make rat model of vascular dementia,and the ability of learning and memory was observed in Morris water maze.Results：The average time of escape and latency in the rats of model group in the water maze test was prolonged,with significant difference compared with that in the sham group （P〈0.01）.The average time of escape and latency and navigation test results of rats pretreated by EA had statistically significant difference compared with those of the model group （P〈0.01）.Conclusion：EA pretreatment can significantly improve the ability of learning and memory of the rats with vascular dementia.

Effects of repetitive transcranial magnetic stimulation on cognitive function and cholinergic activity in the rat hippocampus after vascular dementia

Repetitive transcranial magnetic stimulation （rTMS） is a non-invasive treatment that can enhance the recovery of neurological function after stroke. Whether it can similarly promote the recovery of cognitive function after vascular dementia remains unknown, In this study, a rat model for vascular dementia was established by the two-vessel occlusion method. Two days after injury, 30 pulses of rTMS were ad- ministered to each cerebral hemisphere at a frequency of 0.5 Hz and a magnetic field intensity of 1,33 T. The Morris water maze test was used to evaluate learning and memory function. The Karnovsky-Roots method was performed to determine the density of cholinergic neurons in the hippocampal CA1 region. Immunohistochemical staining was used to determine the number of brain-derived neurotroph- ic factor （BDNF）-immunoreactive cells in the hippocampal CA1 region, rTMS treatment for 30 days significantly improved learning and memory function, increased acetylcholinesterase and choline acetyltransferase activity, increased the density of cholinergic neurons, and increased the number of BDNF-immunoreactive cells. These results indicate that rTMS can ameliorate learning and memory deficiencies in rats with vascular dementia, The mechanism through which this occurs might be related to the promotion of BDNF expression and subsequent restoration of cholinergic system activity in hippocampal CA 1 region.

Panax ginseng extract attenuates neuronal injury and cognitive deficits in rats with vascular dementia induced by chronic cerebral hypoperfusion

Panax ginseng is a slow-growing perennial plant.Panax ginseng extract has numerous biological activities,including antitumor,anti-inflammatory and antistress activities.Panax ginseng extract also has a cognition-enhancing effect in rats with alcohol-induced memory impairment.In this study,we partially occluded the bilateral carotid arteries in the rat to induce chronic cerebral hypoperfusion,a wellknown model of vascular dementia.The rats were then intragastrically administered 50 or 100 mg/kg Panax ginseng extract.Morris water maze and balance beam tests were used to evaluate memory deficits and motor function,respectively.Protein quantity was used to evaluate cholinergic neurons.Immunofluorescence staining was used to assess the number of glial fibrillary acidic protein-positive cells.Western blot assay was used to evaluate protein levels of vascular endothelial growth factor,basic fibroblast growth factor,Bcl-2 and Bax.Treatment with Panax ginseng extract for 8 weeks significantly improved behavioral function and increased neuronal density and VEGF and b FGF protein expression in the hippocampal CA3 area.Furthermore,Panax ginseng extract reduced the number of glial fibrillary acidic protein-immunoreactive cells,and it decreased apoptosis by upregulating Bcl-2 and downregulating Bax protein expression.The effect of Panax ginseng extract was dose-dependent and similar to that of nimodipine,a commonly used drug for the treatment of vascular dementia.These findings suggest that Panax ginseng extract is neuroprotective against vascular dementia induced by chronic cerebral hypoperfusion,and therefore might have therapeutic potential for preventing and treating the disease.

Resveratrol improves cognition and reduces oxidative stress in rats with vascular dementia

Resveratrol possesses beneficial biological effects, which include anti-oxidant, anti-inflammatory and anti-carcinogenic properties. Recently, resveratrol has been shown to exhibit neuroprotective effects in models of Parkinson＇s disease, cerebral ischemia and Alzheimer＇s disease. However, its effects on vascular dementia remain unclear. The present study established a rat model of vascular dementia using permanent bilateral common carotid artery occlusion. At 8-12 weeks after model induction, rats were intragastrically administered 25 mg/kg resveratrol daily. Our results found that resveratrol shortened the escape latency and escape distances in the Morris water maze, and pro- longed the time spent percentage and swimming distance percentage in the target quadrant during the probe test, indicating that resveratrol improved learning and memory ability in vascular dementia rats. Further experiments found that resveratrol decreased malonyldialdehyde levels, and increased superoxide dismutase activity and glutathione levels in the hippocampus and cerebral cortex of vascular dementia rats. These results confirmed that the neuroprotective effects of resveratrol on vascular dementia were associated with its anti-oxidant properties.

Hippocampal expression of synaptic structural proteins and phosphorylated cAMP response element-binding protein in a rat model of vascular dementia induced by chronic cerebral hypoperfusion

The present study established a rat model of vascular dementia induced by chronic cerebral hypoperfusion through permanent ligation of bilateral common carotid arteries.At 60 days after modeling,escape latency and swimming path length during hidden-platform acquisition training in Morris water maze significantly increased in the model group.In addition,the number of accurate crossings over the original platform significantly decreased,hippocampal CA1 synaptophysin and growth-associated protein 43 expression significantly decreased,cAMP response element-binding protein expression remained unchanged,and phosphorylated cAMP response element-binding protein expression significantly decreased.Results suggested that abnormal expression of hippocampal synaptic structural protein and cAMP response element-binding protein phosphorylation played a role in cognitive impairment following chronic cerebral hypoperfusion.

Effects of electroacupuncture versus nimodipine on long-term potentiation and synaptophysin expression in a rat model of vascular dementia

The present study stimulated Baihui （DU 20） and Dazhui （DU 14） acupoints in a rat model of vascular dementia with electroacupuncture to investigate changes in long-term potentiation and synaptophysin expression in the hippocampus. The results revealed that synaptophysin expression in brain tissues was increased after electroacupuncture. After high4requency stimulation, the population spike latency was shortened and the excitatory postsynaptic potential slope and population spike amplitude were increased. In addition, cognitive function was enhanced, similar to the effects of intragastric perfusion of nimodipine. The results indicated that electroacupuncture at Baihui and Dazhui acupoints can improve learning and memory functions of a rat model of vascular dementia by promoting synaptophysin expression, enhancing hippocampal synaptic plasticity and accelerating synaptic transmission.

海马干细胞来源的外泌体对血管性痴呆大鼠学习记忆能力改善作用及其机制探究

目的分析海马干细胞来源的外泌体对血管性痴呆大鼠学习记忆能力改善作用及其机制。方法取新生SD大鼠海马组织,提取海马干细胞外泌体。成年特殊清洁级(SPF)健康雄性SD大鼠90只,随机分为假手术组、模型组及外泌体组,每组30只,检测各组大鼠学习记忆能力、氧化应激因子水平、海马组织病理学变化、海马组织因子、脑微血管密度以及凋亡相关因子变化。结果透射显微镜观察到海马干细胞来源外泌体结构呈圆形或椭圆形杯状结构的小囊泡,其结构完整,直径50~100 nm之间;特异性标记蛋白CD9、CD63表达阳性。与假手术组比较,模型组大鼠逃避潜伏期及错误次数明显延长,平台区域探索时间及有效区停留时间明显缩短,MDA、AchE、ET-1、VEGF、Bax水平均明显升高,SOD、5-HT、Bcl-2水平均明显降低,脑微血管内皮细胞明显减少(P<0.05);与模型组对比,外泌体组大鼠逃避潜伏期明显缩短,平台区域探索时间及有效区停留时间明显延长,MDA、AchE、ET-1、VEGF、Bax水平均明显降低,SOD、5-HT、Bcl-2水平均明显升高,脑微血管内皮细胞明显增多(P<0.05)。假手术组大鼠海马组织细胞排列紧密,结构清晰,大小、形态一致,且具有丰富的尼氏小体;模型组大鼠海马组织细胞排列紊乱,形态、结构不完整,尼氏小体数量明显减少;外泌体组大鼠海马组织较模型组明显改善,细胞形态较模型组明显完整,尼氏小体数量增多。结论海马干细胞来源的外泌体能够明显改善血管性痴呆大鼠的学习记忆能力,对海马神经元损伤起到一定的保护作用,其作用机制可能与抑制氧化应激与细胞凋亡,调控神经递质含量,促进脑微血管密度有关。

沙棘叶多糖对血管性痴呆大鼠学习记忆能力的改善作用

通过建立血管性痴呆大鼠模型,研究沙棘叶多糖对学习记忆能力的影响。设置假手术组、模型组、低、高剂量沙棘叶多糖组(100、200 mg/kg)及尼莫地平组(6.25 mg/kg),干预治疗28 d后检测相关指标变化。结果显示,与模型组比较,低、高剂量沙棘叶多糖组逃避潜伏期降低了24.35%、32.90%(P<0.01),目标象限停留时间增加了24.35%、51.30%(P<0.01),平台穿越次数提升了29.33%、60.58%(P<0.01),且海马组织病理形态减轻;海马组织神经元细胞凋亡率及B淋巴细胞瘤-2(Bcl-2)相关X蛋白(Bax)、半胱氨酸蛋白酶-3(Caspase-3)mRNA表达减少(P<0.01),Bcl-2mRNA表达增加(P<0.05,P<0.01);海马组织谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性及核因子E2相关因子2(Nrf2)、血红素氧合酶-1(HO-1)蛋白表达增加(P<0.05,P<0.01),丙二醛(MDA)含量降低(P<0.01)。以上结果表明,沙棘叶多糖可以通过抗凋亡及抑制氧化应激发挥改善血管性痴呆大鼠学习记忆能力作用,提示其在预防和治疗血管性痴呆方面有一定的应用前景。

交通任督针刺法对血管性痴呆大鼠CA1区脑源性神经营养因子及学习记忆功能的影响

目的:探讨交通任督针刺疗法对血管性痴呆大鼠学习记忆功能及海马CA1区脑源性神经营养因子(BDNF)表达的影响。方法:采用不同时点永久性结扎雄性SD大鼠双侧颈总动脉(改良2-VO)法复制全脑缺血模型,随机分为空白组、假手术组、模型组、针刺组、尼莫地平组;Morris水迷宫评价大鼠造模前与治疗后空间学习记忆功能;苏木精-伊红(HE)染色观察大鼠海马CA1区组织细胞形态学变化;蛋白免疫印迹法(Western Blot)检测BDNF表达。结果:治疗后,模型组定位航行潜伏期明显较空白组及假手术组延长(P<0.05),空间搜索穿越次数较空白组及假手术对照组明显减少(P<0.05);针刺组和尼莫地平组定位航行潜伏期均明显短于模型组(P<0.05),空间搜索穿越次数均明显多于模型组(P<0.05)。海马病理组织HE染色光镜下观察,模型组大量神经元变性,体积变小,胞核与胞浆界限不清,核固缩成三角形或不规则形,核仁消失,血管、神经元及神经胶质细胞周围间隙扩大,针刺组神经元细胞均可见零星损伤细胞,海马锥体细胞层细胞形态、排列基本正常。与模型组相比,针刺组和尼莫地平组BDNF表达明显增加(P<0.05或P<0.01);与空白组及假手术组相比,针刺组与尼莫地平组BDNF表达差异无统计学意义(P>0.05);结论:交通任督针刺法对Morris水迷宫定位航行潜伏期的学习能力和空间搜索穿越次数的记忆能力有一定改善作用,可提高血管性痴呆大鼠海马CA1区BDNF表达,对缺血致大鼠海马神经元细胞损伤有一定的保护作用。

磷酸肌酸钠对VaD老年大鼠的学习记忆能力影响及机制

目的探讨磷酸肌酸钠对血管性痴呆(VaD)大鼠的学习记忆功能的影响及机制。方法72只SD雄性老年大鼠(>20周龄)随机均分为假手术组、模型组及磷酸肌酸钠低(20 mg/kg)、高剂量(40 mg/kg)组,后3组建立VaD大鼠模型,造模后两组大鼠分别腹腔注射相应浓度的磷酸肌酸钠,假手术组和模型组给予等体积生理盐水腹腔注射,连续给药28 d;实验期间观察大鼠体质量和生长趋势,造模第24天时通过Morris水迷宫实验记录各组大鼠逃避潜伏期、穿越平台次数和平台象限活动时间;实验结束时,取各组大鼠海马组织,检测三磷酸腺苷(ATP)、丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)的含量,ELISA法检测海马组织中炎症因子白细胞介素-1β(IL-1β)、IL-6、IL-10及肿瘤坏死因子(TNF-α)的含量;苏木素-伊红(HE)染色观察海马组织结构。结果与模型组比较,磷酸肌酸钠组大鼠的体质量和生长趋势无明显差异;与模型组比较,磷酸肌酸钠高剂量组大鼠的逃逸潜伏期缩短、穿越平台的次数和平台象限活动时间增加,所在目标象限轨迹更长(P<0.05);与模型组比较,磷酸肌酸钠高剂量组大鼠海马区ATP水平以及SOD、GSH-PX活力升高(P<0.05),MDA水平降低(P<0.05);与模型组比较,磷酸肌酸钠高剂量组大鼠IL-1β、IL-6、TNF-α水平下降,IL-10水平升高(P<0.05);与模型组比较,磷酸肌酸钠低剂量组大鼠HE染色的海马区细胞形态较为完整、规则,磷酸肌酸钠高剂量组神经元染色均匀,细胞形态规则,边界清晰且数量增多。结论磷酸肌酸钠腹腔注射,可改善老年VaD模型大鼠的学习记忆能力,其机制可能与提高大鼠海马区ATP的产生,保护VaD老年大鼠海马神经元,减少病理损伤有关。

桑寄生水提物灌胃对血管性痴呆大鼠学习记忆能力的影响及其作用机制

目的观察桑寄生水提物灌胃对血管性痴呆(VD)大鼠学习记忆能力的影响,并探讨其作用机制。方法将健康雄性SD大鼠随机分为假手术组、模型组、桑寄生低剂量组(桑低组)和桑寄生高剂量组(桑高组),每组各8只。模型组、桑低组、桑高组大鼠利用双侧颈总动脉反复缺血再灌注加双侧永久结扎法建立VD模型,假手术组大鼠只分离不结扎动脉,造模后第2天,桑低组、桑高组分别灌胃给予1 g/kg和2 g/kg桑寄生水提物,其他组给予等量蒸馏水,每天1次,连续4周。采用Morris水迷宫实验观察各组大鼠的学习记忆能力;采用WST-1法测定海马组织中超氧化物歧化酶(SOD)活力,采用TBA法测定丙二醛(MDA)含量,采用酶标仪检测乙酰胆碱(Ach)含量。结果在Morris水迷宫定位航行实验中,与假手术组相比,模型组从第3天开始逃避潜伏期延长(P均<0.05);与模型组相比,桑低组从第4天、桑高组从第3天开始大鼠逃避潜伏期降低(P均<0.05)。在空间搜索实验中,模型组比假手术组大鼠的穿台次数减少、游行速度减慢(P均<0.01);与模型组相比,桑低组、桑高组大鼠穿台次数增多,游行速度加快(P均<0.05)。与假手术组相比,模型组的SOD活力降低、MDA含量升高、Ach含量降低(P均<0.05)。与模型组相比,桑高组的SOD活力升高(P<0.05),桑低组与桑高组MDA含量降低、Ach含量增加(P均<0.05)。与桑低组相比,桑高组的SOD活力高(P<0.01),但MDA含量、Ach含量两组相比差异无统计学意义。结论桑寄生水提物对VD大鼠的学习记忆能力有改善作用,其作用机制可能与桑寄生可提高海马组织中SOD活力、增加Ach含量、降低MDA含量有关。

百岁方口服液治疗血管性痴呆的临床观察

目的 :探讨百岁方口服液治疗血管性痴呆 (VD)的疗效。方法 :将符合美国精神病学会DSM IV诊断标准的VD患者 ,按随机数字表分为治疗组 37例 ,对照组 2 8例 ,分别采用百岁方口服液及脑复康治疗 ,疗程 3个月。观察治疗前后患者的临床症状、中医证候变化 ,以及简易智力状态速检表 (MMSE)和日常生活能力量表 (ADL)积分的改变 ,血液流变学、血小板聚集试验、血脂分析等项指标。结果 :临床观察表明百岁方口服液能改善临床症状和中医证候 ,降低血脂 ,改善血液流变性 ,提高患者多种智力量表积分。治疗组显效率 2 4 32 % ,总有效率 75 6 8% ,对照组分别为 10 71% ,6 0 71% ;两组间差异有显著性 (P <0 0 1)。结论 :百岁方口服液能够促进学习记忆的恢复和改善临床症状 ,是治疗血管性痴呆的有效中药制剂。

脑脉泰胶囊对脑缺血再灌大鼠学习记忆功能及脑组织乙酰胆碱含量的影响

目的:探讨脑脉泰胶囊对血管性痴呆(VD)大鼠学习记忆功能及脑组织乙酰胆碱(Ach)含量的影响。方法:通过采用夹闭双侧颈总动脉20min,再灌10min,再夹闭20min的方式制成大鼠VD模型,以水迷宫实验进行学习记忆能力测试;通过采用四血管阻断再灌注法制成大鼠VD模型,以碱性羟胺法测定脑组织Ach含量;并观察脑脉泰胶囊对模型大鼠翻正反射恢复时间的影响。结果:脑脉泰胶囊能明显提高模型大鼠的学习记忆成绩(P<0.05,P<0.01),明显提高脑组织Ach含量(P<0.05,P<0.01),缩短模型大鼠翻正反射恢复时间(P<0.01)。结论:脑脉泰胶囊可能通过提高Ach含量而改善痴呆大鼠的学习记忆能力。

栀子甙对血管性痴呆大鼠行为学和脑组织病理改变的影响

目的观察栀子甙对血管性痴呆(VaD)大鼠认知功能的影响。方法采用双侧颈总动脉结扎制备VaD大鼠模型,予VaD大鼠不同剂量栀子甙〔25mg/(kg·d)、50mg/(kg·d)、75mg/(kg·d)〕灌胃,连续治疗4周后,进行水迷宫实验和脑组织病理检查,结果与假手术组、模型组及多奈哌齐治疗组相比较,观察栀子甙对血管性痴呆大鼠的影响。结果模型组较假手术组大鼠逃避潜伏期延长、平台象限游程/总游程下降(P<0.05);栀子甙高、中剂量治疗组逃避潜伏期短于模型组、平台象限游程/总游程大于模型组(P<0.05),接近于假手术组和多奈哌齐组水平(P>0.05),栀子甙低剂量组与模型组比较未见明显差异,但反映出其具有改善认知损害作用趋势。病理检查显示与模型组相比,栀子甙治疗组大鼠皮层及海马神经元的凋亡坏死明显减轻。结论双侧颈总动脉结扎致慢性低灌注能显著影响大鼠的认知功能,栀子甙对血管性痴呆大鼠模型的认知功能损害有防治作用,具有剂量依赖性。

慢性前脑缺血大鼠学习、记忆功能的研究

摘 要：目的 研究慢性持续性脑血流量下降对大鼠学习、记忆功能的影响。方法 采用双侧颈总动脉永久结扎方法制备慢性前脑缺血动物模型；利用激光多普勒血流仪检测各组大鼠术后不同时间点（术后24h、7d、15d、30d、60d、90d、120d）额叶皮质、海马区局部脑血流量（rCBF）；采用被动回避性条件反射──跳台试验检验各组大鼠（时间点同前）学习能力；利用水迷宫方法检验各组大鼠记忆功能。结果 大鼠术后额叶皮质、海马区的rCBF明显下降，以术后24h最明显，至术后120d时仍明显低于正常，呈慢性持续性下降的趋势。同时各实验组大鼠学习、记忆能力也明显下降，且有随时间推移而逐渐加重的倾向。结论 慢性持续性脑血流量下降可导致实验大鼠出现进行性认知功能障碍。

电针对拟血管性痴呆小鼠脑组织海马细胞凋亡的影响

目的:观察电针对拟血管性痴呆(VD)小鼠海马细胞凋亡及学习记忆的影响,探讨电针治疗VD的作用机制。方法:健康雄性昆明小鼠80只,随机分为假手术组、模型组、电针组、尼莫地平组。采用反复结扎双侧颈总动脉的方法制备VD模型。术后当天动物苏醒后开始治疗,电针组以疏密波、频率2/80Hz、强度2mA刺激"百会""大椎""足三里""膈俞"10min;尼莫地平组灌服尼莫地平液30mg/kg。两组均每日治疗1次,连续15d。治疗结束后进行行为学检测,Tunel法检测海马细胞凋亡表达。结果:模型组小鼠学习与记忆成绩较假手术组均显著降低(P<0.01),电针组和尼莫地平组较模型组均显著提高(P<0.01,P<0.05),且电针组对小鼠记忆能力的改善优于尼莫地平组(P<0.01,P<0.05);模型组凋亡细胞数目明显多于假手术组(P<0.01),电针组及尼莫地平组均见少量凋亡细胞,明显少于模型组(P<0.01,P<0.05)。结论:电针治疗可显著提高VD小鼠的学习记忆能力,其作用机制可能与抑制脑组织海马细胞过度凋亡,促进受损神经元修复有关。

交泰丸对血管性痴呆模型大鼠学习记忆能力及脑组织胆碱能机制的影响

目的研究交泰丸对血管性痴呆(VD)大鼠学习记忆及脑组织胆碱能机制的影响,探讨其对VD治疗的作用及机制。方法采用线栓法制备VD大鼠模型,MG-2Y迷宫进行行为学测试,羟胺比色法测定脑组织乙酰胆碱(Ach)含量,分光光度法测定脑组织乙酰胆碱酯酶(AchE)活性,HE染色观察海马区病理变化。结果模型对照组大鼠学习记忆能力明显劣于假手术组,Ach含量降低,AchE活性升高,海马区病理改变严重;交泰丸治疗后,尤其是高剂量交泰丸组,学习记忆能力明显提高,Ach含量升高,AchE活性降低,海马区病理变化明显改善。结论交泰丸对VD大鼠学习记忆能力下降有明显的保护作用,其作用机制可能与抑制AchE活性,提高Ach含量,修复及保护缺血再灌注VD大鼠海马区神经元密切相关。