Effects of special brain area regional cerebral blood flow abnormal perfusion on learning and memory function and its molecular mechanism in rats

To study the effect of special brain area regional cerebral blood flow (rCBF) abnormal perfusion on learning and memory function and its molecular mechanism, 64 adult male healthy Sprague-Dawley (SD) rats were randomly divided into two groups, the false operation group (control group) and the operation group (model group). After surgical operation, the operation group undertook bilateral common carotid artery permanent ligation, while the other group did not. Learning and memory function were measured by Y-maze at 4 h, 8 h, 24 h and 3 d after surgical operation, respectively. The rCBF of the right frontal lobe and hippocampus was also detected by the PerifluxPF model laser Doppler flowmetry, and the expressions of c-fos or c-jun or Bcl-2 and Bax were also measured by immune histochemistry S-P method accordingly. Results showed that the rCBF of the right frontal lobe and hippocampus in the operation group was significantly lower than that in the false operation group (P < 0.05). The learning indexes, error number (EN), day of reach standard and total reaction time (TRT) in the operation group, were significantly higher than that in the false operation group (P < 0.05). However, the initiative evasion rate in the operation group was significantly lower than that in the false operation group. The study also found that the rCBF was relatively more, the indexes (EN, the day of reach standard and TRT) relatively fewer, but the initiative evasion rate and the memory keeping rate were relatively more. The positive expression and the average absorbency of Fos and Jun in the operation group were significantly higher than that in the false operation group (P < 0.05). Furthermore, Bax and Bcl-2 positive cells were all increased over time in the operation group, and the expression ratio of Bax/Bcl-2 in the operation group was significantly higher than that in the false operation group (P < 0.01). In conclusion, rCBF decrease can impair the learning and memory function in rats, which may be related to the increase of the expression ratio of c-fos or c-jun or Bcl-2 or Bax in the frontal cortex and hippocampus.     

Effects of selenium and iodine on c-fos and c-jun mRNA and their protein expressions in cultured rat hippocampus cells

The objective of the study was to investigate the effect of selenium (Se) and iodine (I) for expressions of c-fos and c-jun mRNA and their proteins in cultured rat hippocampus cells in selenium- and iodine-containing medium. With cultured rat hippocampus cells, the different doses of Se and I were added into the medium. The expressions of c-fos/c-jun in cultured rat hippocampus cells (1 d, 3 d, 5 d, 7 d, and 10 d) were studied by using both in situ hybridization histochemistry and SABC immunohistochemistry techniques. Both Se and I could enhance expressions of c-fos and c-jun mRNA and their proteins, especially c-jun mRNA expression in the Se and I united group. Se and I could promote the expressions of c-fos and c-jun and thus may affect the differentiation and development of hippocampus neurons.     

辣木叶对糖尿病大鼠认知功能及海马神经细胞凋亡的影响*

目的:探讨辣木叶对链脲佐菌素(STZ)诱导的糖尿病模型大鼠认知功能障碍及海马神经细胞凋亡的影响。方法:选取健康SD雄性大鼠50只,随机选取10只作为对照组,40只大鼠给予腹腔注射25 mg/kg STZ构建糖尿病大鼠模型。40只大鼠随机分为模型组、辣木高、中、低剂量组,分别每日灌胃给药2.0 g/kg、4.0 g/kg、8.0 g/kg辣木叶,对照组和模型组每日灌胃给药等量生理盐水,1次/日,持续给药8周。Morris水迷宫实验评价大鼠学习记忆能力;HE染色及免疫组化染色对大鼠海马神经元切片进行染色,观察各组大鼠海马神经元病理改变的情况及Bax、caspase-3及Bcl-2蛋白表达情况;酶联免疫法(ELISA)检测大鼠海马组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)。结果:与对照组相比,模型组大鼠血糖值明显提高(P＜0.01),血胰岛素水平明显降低(P＜0.05);与模型组相比,辣木组血糖值显著降低(P＜0.05,P＜0.01),辣木中、高剂量组血胰岛素水平显著升高(P＜0.05,P＜0.01)。不同剂量组辣木组间比较,给药后3组大鼠FBG及INS无统计学差异(P＞0.05);Morris水迷宫实验的第4-5日,与模型组相比较,辣木各剂量组潜伏期均明显缩短(P＜0.05);辣木不同剂量组目标象限停留时间明显延长(P＜0.05)。炎症因子变化结果,与模型组相比较,辣木低、中、高剂量组TNF-α、IL-6含量及蛋白表达水平显著降低(P＜0.05)。HE染色及免疫组化染色结果显示,与模型组相比较,辣木中剂量组中阳性表达,呈棕黄色,细颗粒状。辣木叶中剂量组(53.21±7.19)能显著减少神经元细胞凋亡的数目(P＜0.01);辣木组中剂量组大鼠海马组织中Bax、caspase-3的蛋白表达及Bax/Bcl-2比例显著降低(P＜0.05)。结论:辣木叶能改善糖尿病大鼠认知功能障碍其作用机制可能与调节Bax、Bcl-2、caspase-3的蛋白表达,降低炎症因子TNF-α及IL-6含量相关。     

艾灸对阿尔茨海默病模型大鼠血脑屏障结构与学习记忆功能的影响*

目的:探讨艾灸对阿尔茨海默病(AD)模型大鼠血脑屏障结构与学习记忆功能的影响。方法:48只SD大鼠随机分为4组:正常对照组、假手术组、模型组、艾灸组,模型组和艾灸组大鼠采用双侧海马一次性注射聚集态Aβ_25-35的方法建立AD大鼠模型,假手术组双侧海马区注射等量生理盐水,正常组不做处理。造模成功后,在艾灸组大鼠的“百会”、“肾俞”、“印堂”穴上方2～3 cm处施予艾条温和灸治疗,每穴10 min,每天1次,持续治疗21 d。采用Morris水迷宫实验评估各组大鼠的学习与记忆能力,伊文思蓝法检测血脑屏障通透性,电镜下观察血脑屏障的超微结构,免疫组化法检测海马区MMP-2和MMP-9阳性细胞数。结果:与正常对照组和假手术组比较,模型组大鼠逃避潜伏期时间显著增加(P＜0.01),空间探索时间显著下降(P＜0.01),学习记忆功能严重受损,脑内伊文思蓝含量显著增加(P＜0.01),血管周围水肿变大,血脑屏障结构功能受损,同时海马MMP-2和MMP-9阳性表达均显著增加(P＜0.01);与模型组比较,艾灸治疗组大鼠的学习与记忆能力均有所增强(P＜0.05),脑内伊文思蓝含量显著下降(P＜0.05),血管周围水肿程度减轻,血脑屏障损伤情况得到改善,海马MMP-2和MMP-9阳性表达显著降低(P＜0.05或P＜0.01)。结论:艾灸能减轻AD模型大鼠血脑屏障结构的损伤程度,从而改善大鼠的学习记忆能力,其机制可能与MMP-2和MMP-9被抑制有关。     

姜黄素对过度训练致大鼠脾脏细胞凋亡的调控作用及其机制*

目的:研究姜黄素调控Keap1-Nrf2-ARE信号通路缓解大鼠过度训练所致脾脏氧化应激及细胞凋亡机制。方法:7周龄SPF级雄性Wistar大鼠分为对照组(C组,n=12)、过度训练组(OM组,n=11)、姜黄素+过度训练组(COM组,n=14)。C组不进行任何运动干预,OM组、COM组大鼠进行8周递增负荷游泳训练。训练期间,COM组以200 mg/(kg·d)、5 ml/kg姜黄素进行灌胃,其他组灌胃等体积0.5 %羧甲基纤维素纳助溶剂。末次训练后24 h,称重计算脾脏指数,光镜观察脾脏组织病理学改变,取血液、脾脏组织检测相关生化指标。结果:C组大鼠脾脏组织结构正常;OM组较C组脾脏指数极显著降低(P＜0.01),并出现明显病理学改变;COM组较OM组脾脏指数显著升高(P＜0.05),且组织形态学改变有所改善。与C组比较,OM组血清皮质酮(Cor)浓度和脾脏细胞凋亡水平、丙二醛(MDA)浓度均升高,促凋亡蛋白Bcl-2相关X蛋白(Bax)表达增强(P＜0.05或P＜0.01);体重、血清睾酮(T)水平及脾脏超氧化物歧化酶(SOD)活性降低,脾脏血红素氧合酶1(HO-1)、抗凋亡蛋白B淋巴细胞瘤因子-2(Bcl-2)表达减弱(P＜0.05或P＜0.01);脾脏核因子E2相关因子2(Nrf2)表达水平无显著变化(P＞0.05)。与OM组比较,COM组体重无显著变化(P＞0.05);血清T浓度升高,脾脏SOD活性升高,Bcl-2、Nrf2和HO-1表达增强(P＜0.05或P＜0.01);血清Cor浓度及脾脏MDA浓度、细胞凋亡水平、Bax表达均降低或减弱(P＜0.05或P＜0.01);组间T/Cor比值变化趋势与T变化相一致,Bcl-2/Bax比值变化趋势与Bcl-2变化相一致。结论:8周递增负荷过度游泳训练引发脾脏细胞凋亡加剧,脾脏组织发生病理改变及功能异常。姜黄素通过上调Nrf2、HO-1蛋白表达,在一定程度上缓解过度训练引发的氧化应激,增强抑凋亡蛋白Bcl-2表达,减弱促凋亡蛋白Bax表达,改善大鼠脾脏细胞过度凋亡,保护脾脏组织结构和功能正常。     

二氢杨梅素改善慢性社会挫败应激小鼠认知与情感障碍*

目的:探索二氢杨梅素(DHM)对慢性社会挫败应激小鼠认知与情感障碍的作用及其可能机制。方法:将C57BL/6J小鼠随机分成对照组(Control)、慢性社会挫败应激组(CSDS)和慢性社会挫败应激+DHM组(CSDS+DHM),每组14只,每天将两个应激组小鼠放入ICR攻击鼠的饲养笼中10 min,之后取出放于ICR攻击鼠饲养笼的旁边笼中,连续应激10 d,在应激5 d后,每天按10 ml/kg的量分别腹腔注射一次2%的DMSO或20 mg/kg的DHM(分散于2% DMSO中),连续注射5 d,之后每组取10只小鼠进行新颖物体识别测试、Y迷宫测试、社会交互和旷场测试、行为学测试,剩余4只小鼠于实验结束后24 h内断头取脑,采用Western blot法检测海马组织SIRT1水平。结果:与Control组比较,CSDS组小鼠的学习记忆显著降低,焦虑水平显著升高,在悬尾测试(TST)和强迫游泳测试(FST)中的不动时间显著升高,海马SIRT1蛋白水平显著降低(P均＜0.05或P＜0.01);与CSDS组比较,CSDS+DHM组小鼠学习记忆显著提高,小鼠焦虑水平显著降低,在TST和FST中不动时间显著降低,海马SIRT1蛋白水平显著升高(P均＜0.05或P＜0.01)。结论:DHM可改善CSDS诱导小鼠的认知障碍、焦虑样行为和抑郁样行为,并提高海马SIRT1蛋白的表达水平。     

参麦注射液对肠缺血/再灌注肺损伤大鼠肺组织p38MAPK及凋亡相关基因表达的影响

目的:观察参麦注射液(SM)对肠缺血/再灌注(I/R)肺损伤大鼠肺组织p38MAPK和凋亡相关基因Bax、Bcl-2蛋白表达的影响,探讨其保护机制。方法:采用夹闭肠系膜上动脉(SMA)方法建立大鼠肠I/R损伤模型。24只SD大鼠随机分为对照组(Control组)、肠缺血/再灌注组(I/R组)、参麦注射液组(SM+I/R组),每组8只。比较各组大鼠肺湿/干比(W/D)、肺表面活性物质主要成分卵磷脂(PC)及总磷脂(TPL)含量的变化;同时免疫组织化学法检测各组大鼠肺组织中p38MAPK、Bax及Bcl-2蛋白的表达水平。结果:与对照组比较,I/R组肺组织W/D明显升高,而PC和TPL的含量显著降低,肺组织p38MAPK、Bcl-2和Bax蛋白表达明显增强(P均＜0.01),其中Bax的增强比Bcl-2的增强更为明显,Bcl-2/Bax比值降低(P＜0.01);与I/R组比较,SM+I/R组大鼠肺组织W/D明显降低,PC和TPL的含量增加,肺组织p38MAPK和Bax蛋白表达下降(P均＜0.01),Bcl-2的表达增强,Bcl-2/Bax比值明显升高(P＜0.01)。相关分析显示,肠I/R时肺组织p38MAPK蛋白表达水平与肺表面活性物质主要功能成分PC含量及凋亡基因Bcl-2/Bax比值呈负相关(r分别为-0.787,-0.731,P均＜0.01)。结论:SM可能通过抑制p38MAPK信号通路的激活,提高Bcl-2/Bax比值来阻抑细胞凋亡,从而减轻肠I/R时的肺损伤。     

Aminoguanidine Changes Hippocampal Expression of Apoptosis-Related Genes,Improves Passive Avoidance Learning and Memory in Streptozotocin-Induced Diabetic Rats

Cognitive dysfunction occurs in patients with diabetes mellitus. The objective of this study was to examine whether bilateral intrahippocampal CA1 (intra-CA1) injection of aminoguanidine (AG) can either affect the Bcl-2 family gene expression or reduce the diabetic imposing abnormalities of passive avoidance learning (PAL) and memory. Rats were divided into five groups: control (C), control treated with normal saline (CS), control treated with AG (S-AG), diabetics (D), and diabetics treated with AG (D-AG). Diabetes mellitus was induced by a single intraperitoneal injection of streptozotocin (STZ) (50 mg/kg). AG (30 μg/rat) or vehicle was administered intra-CA1 bilaterally at the onset of hyperglycemia. PAL was assessed 7 weeks later. Animals were killed, and hippocampus was dissected following the behavioral test. The expressions of Bax, Bcl-2, and Bcl-xl mRNAs were measured using semiquantitative RT-PCR technique. The result of passive avoidance task showed that AG significantly improved the cognitive performance in diabetic rats. Moreover, AG treatment decreased the levels of Bcl-2 and Bcl-x_L expressions in diabetic group. The ratio of Bax/Bcl-2 and Bax/Bcl-x_L decreased significantly in AG-treated diabetic animals. In conclusion, initial treatment with AG by intra-CA1 micro-injection improves the impaired passive avoidance task in STZ-induced diabetic rats which may be related to the decreased Bax/Bcl-2 and Bax/Bcl-x_L ratios.     

电针对大鼠局灶性脑缺血后脑内Bax,Bcl-2表达的影响

为了探讨 bcl- 2基因家族成员 bax,bcl- 2的表达产物 Bax、 Bcl- 2与电针抗缺血脑损伤的关系。本实验采用改良线拴法制备大鼠大脑中动脉 (MCA )阻塞 -再灌注模型 ,并用 TTC及 HE染色观察缺血及电针后梗塞灶的变化 ,用免疫组织化学方法对大鼠局灶性脑缺血组织内 Bax,Bcl- 2免疫阳性细胞的分布及电针对该分布的影响进行观察。发现 :1.行为生理学观察 :电针组大鼠神经缺损 Bederson综合评分明显低于缺血组综合评分 (P<0 .0 5 ) ;2 .TTC染色表明梗塞灶中心位于尾壳核 ,累及大脑皮层 ;HE染色计算缺血组梗塞灶体积为 74.72± 3.6 7m m3,电针组为 5 2 .6 6± 1.81mm3,两组间有显著性差异 (P<0 .0 1) ;3.大鼠 MCA阻塞 30 m in再灌注 48小时后 ,缺血组及电针组梗塞灶中心 (尾壳核 )偶见 Bax及 Bcl- 2免疫阳性细胞 ;缺血组半影区 Bax阳性细胞数量显著增加 (P<0 .0 1)。 Bcl- 2免疫阳性细胞数反应性上调 (P<0 .0 5 ) ;电针组半影区 Bax的表达与缺血组相比下调 (P<0 .0 5 ) ,但仍高于对照组 (P<0 .0 5 ) ;Bcl- 2的表达与缺血组之间无差异显著性。海马 CA1区神经元 Bax,Bcl- 2的表达在各组间均无显著性差异。结果表明电针有抗缺血脑损伤的效应 ,其分子机制之一可能是通过下调半影区 Bax的表达而相对降低 Bax/Bcl- 2比     

Hydrogen Sulfide Attenuates Neuronal Injury Induced by Vascular Dementia Via Inhibiting Apoptosis in Rats

Hydrogen sulfide (H₂S) is a gaseous messenger and serves as an important neuromodulator in the central nervous system. The current study was undertaken to investigate whether H₂S attenuates the neuronal injury induced by vascular dementia (VD). Rats were subjected to bilateral common carotid artery and vertebral artery occlusion for 5 min three times in an interval of 5 min to induce VD. An H₂S donor, sodium hydrosulfide (NaHS) or an inhibitor of cystathionine-β-synthase, hydroxylamine (HA) was administered intraperitoneally. The number of neurons in the hippocampus was determined by hematoxylin and eosin staining, and the performance of learning and memory was tested by the Morris water maze. H₂S content in plasma was evaluated. Apoptosis in the hippocampus was assessed by flow cytometry. In addition, Bcl-2 and Bax expression was analyzed by immunohistochemical staining. The neuronal injury occurred gradually with a decreased number of neurons and increased apoptosis ratio in the hippocampus over 720 h after VD. The H₂S level was also gradually decreased in plasma over 720 h after VD, which negatively correlated with the apoptosis ratio in the hippocampus after VD. In addition, NaHS treatment significantly attenuated neuronal injury and improved neural functional performance, whereas HA exaggerated the neuronal injury and exacerbated learning and memory at 720 h after VD. Furthermore, NaHS treatment markedly improved the ratio of Bcl-2 over Bax with increased Bcl-2 expression and decreased Bax expression. In contrast, HA reduced the ratio of Bcl-2 over Bax. It is suggested that H₂S attenuates VD injury via inhibiting apoptosis and may have potential therapeutic value for VD.     

The Analog of Ginkgo biloba Extract 761 is a Protective Factor of Cognitive Impairment Induced by Chronic Fluorosis

Ginkgo biloba extract EGb761 is widely used to treat patients with learning and memory impairment in Alzheimer’s disease and Parkinson’s disease in China. However, it is not yet clear whether the analog of EGb761 (EGb) has a protective effect on the learning and memory damage induced by chronic fluorosis. In this study, 30 Wistar rats were randomly divided into three groups: a control group, a sodium fluoride (NaF) + EGb group, and a NaF group. The rats were administered 0.5 ml water containing NaF (100 mg/l) and EGb (120 mg/kg) per day via gavage. After 3 months, the rats’ capacity for learning and memory was tested using a Y-maze. Damage to hippocampal neurons was evaluated by histological examination of the CA3 area. Superoxide dismutase (SOD) activity and the levels of glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were measured. Furthermore, the expression levels of Bcl-2 and Bax and the levels of cleaved Caspase3 in the hippocampus were evaluated by RT-PCR and Western blotting. The results showed that EGb could improve learning and memory abilities, enhance the activities of SOD and GSH-Px, attenuate the level of MDA, upregulate the ratio of Bcl-2/Bax, and downregulate the level of cleaved Caspase3.     

APP5肽对糖尿病小鼠学习记忆功能与海马神经元蛋白表达的影响

目的研究APP5肽对糖尿病模型小鼠学习记忆能力及海马神经元蛋白表达的影响。方法用链脲佐菌素诱发小鼠糖尿病模型,应用APP5肽（0.0014 mg/kg）皮下注射治疗,5周后进行Morris水迷宫试验;小鼠脑组织海马做Akt、PI3K、P-CREB、Bcl-2、Bax、CytoC免疫组织化学染色;另一部分鼠脑海马,做Bcl-2、Bax抗体蛋白免疫印记。结果（1）水迷宫试验：糖尿病模型小鼠到达站台游动时间比正常对照组延长（P〈0.01）;而APP5肽皮下注射治疗组较DM组动物分别缩短（P〈0.01）。（2）神经免疫组织化学实验和Western blot：给予APP5肽糖尿病小鼠与对照组小鼠海马组织内神经元表达细胞存活相关蛋白及抗凋亡相关蛋白PI3K、Akt、P-CREB、Bcl-2阳性细胞数相似,明显高于糖尿病小鼠（P〈0.01）;APP5肽给予糖尿病小鼠与对照组小鼠表达凋亡蛋白Bax、cytoC阳性细胞数相似,明显少于糖尿病小鼠（P〈0.01）。Western blot结果相同。结论糖尿病小鼠海马神经元表达细胞存活相关蛋白下降,神经元表达细胞凋亡相关蛋白增加,导致其学习记忆能力下降。APP5肽应用可以使上述蛋白恢复到接近正常,从而改善糖尿病小鼠学习记忆能力。     

硫氢化钠对脊髓小脑共济失调3型小鼠海马MBP及学习记忆的影响

目的: 探讨硫氢化钠(NaHS)对脊髓小脑共济失调3型(SCA3)小鼠海马神经元髓鞘碱性蛋白(MBP)及学习记忆的影响及其治疗意义。方法: 随机挑选12只雄性正常野生型小鼠(WT)作为正常对照组(NC Group),然后将48只SCA3小鼠随机分为SCA3模型组(M Group)、低剂量小鼠组(NL Group,10 μmol/kg)、中剂量小鼠组(NM Group,50 μmol/kg)和高剂量小鼠组(NH Group,100 μmol/kg),每组12只,用药组每日腹腔注射一次,连续4周。通过Morris水迷宫比较不同剂量NaHS干预前后SCA3小鼠学习记忆能力的变化,分光光度法测定海马内硫化氢(H₂S)含量,免疫组化技术检测髓鞘碱性蛋白(MBP)的表达差异,并借助电镜观察各组小鼠神经元髓鞘形态学变化。 结果:与对照组小鼠比较,SCA3小鼠的学习记忆能力显著下降(P＜0.05),海马内H₂S含量降低(P＜0.05),有髓神经纤维MBP表达量也降低(P＜0.05),经过不同剂量的外源性NaHS治疗后,学习记忆能力有不同程度改善(P＜0.05);且SCA3小鼠海马H₂S和MBP含量也有不同程度提高(P＜0.05)。结论: 外源性NaHS可能通过提高SCA3小鼠大脑海马的H₂S含量和MBP含量增加,对神经元细胞产生一定的保护作用,进而提高SCA3小鼠的学习记忆能力,为寻求SCA3的治疗提供新的思路,同时为临床SCA3患者的营养支持及治疗提供方向。     

Silencing lncRNA PVT1 inhibits activation of astrocytes and increases BDNF expression in hippocampus tissues of rats with epilepsy by downregulating the Wnt signaling pathway

The aim of this study is to investigate the effects of long-chain noncoding RNA plasmacytoma variant translocation 1 (PVT1) on the activation of astrocytes and the expression of brain-derived neurotrophic factor (BDNF) in hippocampus tissues of epileptic rats. The epilepsy rat model was induced by intraperitoneal injection of lithium chloride–pilocarpine. Successfully modeled rats were grouped, and their spatial learning and memory, neuronal loss, number of TdT-mediated dUTP nick labeling (TUNEL)-positive cells, and the expression of cleaved-caspase-3, pro-caspase-3, Bax, Bcl-2, GFAP, BDNF, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, axin, and cyclin D1 in hippocampus tissues were evaluated. Increased expression of PVT1 was found in hippocampus tissues of epileptic rats. Silencing of PVT1 improved spatial learning and memory, decreased neuronal loss, decreased the number of TUNEL-positive cell, decreased the expression of cleaved-caspase-3 and Bax while increased pro-caspase-3 and Bcl-2 expression, decreased the expression of GFAP, increased the expression of BDNF, decreased the expression of TNF-α, IL-1β, and IL-6, and decreased the expression of axin and cyclin D1 in hippocampus tissues in epileptic rats. Our study provides evidence that the inhibition of PVT1 may decrease the loss of neurons, inhibit the activation of astrocytes, and increase the expression of BDNF in hippocampus by downregulating the Wnt signaling pathway.     

七氟醚对血管痴呆性大鼠海马区细胞凋亡及Bcl-2蛋白表达的影响及相关机制研究

摘要 目的：探讨与研究七氟醚对血管性痴呆（Vascular dementia,VaD）大鼠海马区细胞凋亡及B淋巴细胞瘤-2(B-cell lymphoma-2,Bcl-2)蛋白表达的影响及相关机制。方法：60只老年雄性SD大鼠随机平分为两组-七氟醚与对照组,两组大鼠都采用双侧颈动脉缺血再灌注法制作VaD模型,七氟醚组与对照组在建模前分别吸入0.11 %七氟醚与空气各45 min,分别于建模后7 d、14 d与21 d进行Morris水迷宫实验检测大鼠的逃避潜伏期;建模后21 d,采用TUNEL法测定各组大鼠海马组织细胞凋亡情况,采用黄嘌呤氧化酶法、硫代巴比妥酸法分别测定血清超氧化物歧化酶（Superoxide dismutase,SOD）活性与丙二醛（Malondialdehyde,MDA）含量,采用Western blot法检测Bax、Bcl-2蛋白相对表达水平。结果：两组各有26只大鼠顺利建立VaD模型,建模后7 d、14 d与21 d,七氟醚组的逃避潜伏期均显著少于对照组(P<0.05);建模后21 d,七氟醚组大鼠海马组织神经元细胞凋亡指数显著低于对照组(P<0.05);建模后21 d,七氟醚组大鼠血清SOD活性显著高于对照组,而MDA含量则显著低于对照组(P<0.05);建模后21 d,七氟醚组大鼠海马组织Bax、Bcl-2蛋白的相对表达水平均显著高于对照组(P<0.05)。结论：七氟醚干预可通过促进VaD大鼠海马组织抗凋亡蛋白Bcl-2表达抑制细胞凋亡,并可平衡大鼠的氧化应激反应水平,从而促进大鼠记忆功能恢复正常。     

染料木素对卵巢切除大鼠学习记忆能力的影响

目的：探讨染料木素对卵巢切除大鼠学习记忆能力的影响及作用机制。方法：将40只SD雌性大鼠随机分为用假手术组、去卵巢对照组、染料木素高剂量、低剂量组、17β-雌二醇组,切除卵巢建立学习和记忆能力受损的模型。灌胃给药6周后Morris水迷宫测定各组大鼠学习记忆能力,免疫组化法观察大鼠海马微管相关蛋白（tau蛋白）阳性表达情况,测定大鼠脑组织中乙酰胆碱酯酶（AchE）、乙酰胆碱转移酶（ChaT）、超氧化物歧化酶（SOD）的活性及丙二醛（MDA）的含量,观察海马组织超微结构变化。结果：大鼠切除卵巢后Morris水迷宫测定的学习记忆能力显著下降,微管相关蛋白（tau蛋白）异常磷酸化阳性表达率增高,前脑皮质中超氧化物歧化酶（SOD）、乙酰胆碱转移酶（ChaT）活性降低,丙二醛（MDA）含量、乙酰胆碱酯酶（AchE）活性增高。低剂量的染料木素可以发挥类雌激素样作用,改善去卵巢大鼠的以上症状。结论：染料木素对卵巢切除导致的学习和记忆能力下降有改善作用,低剂量效果显著,其可能的机制是：抑制了脑内AchE的活性,使乙酰胆碱的降解减少;增强脑组织抗氧化能力;稳定微管相关蛋白（tau蛋白）,降低tau蛋白异常磷酸化水平。     

突触功能障碍大鼠模型EE G 频域特征

本文旨在探讨突触功能障碍大鼠模型在额叶、颞叶和海马这些与认知功能有关的脑区EEG频域特征。先用海马CA1区Aβ1-40加微量注射法制备突触功能障碍模型,用Morris水迷宫行为学测试系统检测其学习记忆能力;然后记录上述脑区的EEG并做频谱分析。结果显示：（1）模型组在第3,4、5、6训练时间段的平均逃避潜伏期较正常组明显延长,和第2训练时间段的相比较,正常组第5训练时间段平均逃避潜伏期明显缩短,模型组到第7训练时间段平均逃避潜伏期开始明显缩短（P〈0．05）;撤去平台后,模型组在原平台所在象限的时间百分比明显降低（P〈0．05）。（2）模型组的EEG表现为α节律慢化,功率下降,其主峰频率左移2Hz,并且额叶、颞叶和海马的δ波和θ波功率不同程度地增高。由此Aβ1-40微量注射法成功制备了突触功能障碍大鼠模型。该模型大鼠的学习记忆能力降低,其频谱特征表现为α节律慢化,功率下降或消失,慢波（δ波和θ波）活动增多,功率不同程度地增高。这些与阿尔茨海默病（Alzheimer’s disease,AD）的EEG一致,可为以后对突触功能障碍时受累皮层进行深入的可塑性和神经再生的研究提供电生理基础。