艾司氯胺酮通过激活CREB/BDNF信号通路减轻抑郁症大鼠海马神经元损伤

目的 探究艾司氯胺酮基于环磷腺苷效应元件结合蛋白(CREB)/脑源性神经营养因子(BDNF)信号通路对抑郁症大鼠海马神经元损伤的影响。方法 72只Wistar雄性大鼠随机分为空白组、模型组、帕罗西汀组(10 mg/kg腹腔注射)、艾司氯胺酮组(15 mg/kg腹腔注射)、k252a组(CREB抑制剂,20μl/kg脑内注射)、艾司氯胺酮+k252a组。通过旷场实验、糖水消耗试验对大鼠行为学进行观察;通过酶联免疫吸附试验(ELISA)检测大鼠海马组织5-羟色胺(HT)、多巴胺(DA)、去甲肾上腺素(NE)表达水平;苏木素-伊红(HE)染色和尼氏(Nissl)染色法观测大鼠海马神经元损伤情况;免疫组化法观察大鼠海马组织BDNF表达情况;Western印迹检测大鼠海马组织CREB、BDNF通路表达情况。结果 与空白组相比,模型组神经元损伤加重,水平运动得分、垂直运动得分、糖水偏好率,海马组织匀浆5-HT、DA、NE水平,海马组织CREB、p-CREB、BDNF水平明显下降,停留不动时间明显增长(均P<0.05);与模型组相比,帕罗西汀组、艾司氯胺酮组神经元损伤减轻,水平运动得分、垂直运...     

丁苯酞对糖尿病大鼠认知功能及PKA-CREB通路的影响

目的旨在研究丁苯酞对链脲佐菌素(STZ)所诱导的糖尿病模型大鼠认知功能障碍的治疗作用并探讨其相关作用机制。方法雄性SD大鼠随机分为对照组、模型组及治疗组。对照组大鼠给予柠檬酸盐缓冲剂,模型组及治疗组大鼠腹腔注射STZ诱导糖尿病模型(注射72 h后血糖仪测尾静脉血糖>16. 7 mmol/L视为糖尿病模型制作成功),治疗组给予丁苯酞灌胃治疗,模型组及对照组给予等体积植物油灌胃。连续治疗6 w后进行水迷宫测试检测大鼠学习和记忆功能,检测治疗前后各组血糖水平,Western印迹方法检测大鼠海马蛋白激酶(PK) A、环磷腺苷效应元件结合蛋白(CREB)、脑源性神经营养因子(BDNF)蛋白水平的表达。结果模型组及治疗组与对照组相比逃避潜伏期显著延长,跨越平台次数显著减少(P<0. 05),并伴随着海马PKA、p-CREB和BDNF水平的下降(P<0. 05);治疗组与模型组相比,逃避潜伏期显著缩短,跨越平台次数显著增加(P<0. 05),PKA、p-CREB和BDNF表达显著升高(P<0. 05)。结论丁苯酞治疗可以改善STZ诱导的糖尿病模型大鼠的学习和记忆能力,其机制可能与海马PKA-CREB信号通路的激活密切相关。     

BDNF信号通路调节学习记忆的研究进展

<正>神经营养因子是一类内源性、小型的分泌蛋白,具有促进神经元存活和分化及调节突触生长和发育的功能~([1,2])。哺乳动物脑区的神经营养因子主要有以下几类:脑源性神经营养因子(BDNF)、神经生长因子(NGF)、神经营养素(NT)-3及NT-4/5[3]等。BDNF在中枢神经系统内表达,在哺乳动物脑内含量最多,主要分布于海马和皮质组织等关键脑区,其中以海马CA3区最为富集~([4～6])。BDNF在基因转录翻译过程中,首先形成32 kD的前体蛋白p     

bFGF对拟血管性痴呆小鼠学习记忆及海马5-HT和DA的影响

目的 探讨碱性成纤维细胞生长因子(bFGF)对拟血管性痴呆(VD)小鼠学习记忆的影响及其机制.方法 清醒小鼠反复脑缺血再灌注法建立VD动物模型;造模后给予bFGF干预治疗;采用跳台法、避暗法及Morris水迷宫检测小鼠的学习记忆能力,用荧光分光光度法检测脑组织5-羟色胺(5-HT)和多巴胺(DA)含量,HE染色观察病理形态学变化.结果 bFGF组小鼠学习记忆能力提高(P＜0.01);海马5-HT和DA含量增加(P＜0.05,P＜0.01).结论 bFGF通过调节脑神经递质5-HT和DA含量改善拟VD小鼠学习记忆能力.     

电针对抑郁症大鼠海马CREB-BDNF受体后信号转导通路的作用

目的 探讨电针对抑郁症大鼠的治疗作用及海马cAMP反应元件结合蛋白(CREB)、脑源性神经营养因子(BDNF)的影响.方法 SD成年大鼠32只随机分为空白组、模型组、针刺组(合谷+太冲)和药物组(盐酸氟西汀),每组8只.空白组进行正常饲养,不给予其他处理;模型组大鼠采用长期不可预见性温和刺激造成抑郁症模型;电针组大鼠造模后电针合谷穴和太冲穴,每日1次,每次15 min,左右两侧穴位交替进行,持续21 d.药物组大鼠造模后进行氟西汀灌胃,每日1次,持续3 w.应激后第7、14、22天观察大鼠Open field行为学的变化,应激后22 d取材观察海马神经元形态结构、BDNF和CREB的表达.结果 (1)应激后第7、14、22天模型组大鼠水平运动及垂直运动较应激前有不同程度的减弱,针刺组于应激后第14天可有效地改善抑郁型大鼠模型的行为学表现,其效果优于药物组(P<0.05).(2)模型组海马齿状回神经元排列散乱,可见明显肿胀、固缩、变性、脱落等病理改变;针刺组和药物组大鼠海马神经元的病变程度较模型组有不同程度的减轻.(3)模型组大鼠BDNF阳性细胞数量较空白组明显减少(P<0.05),针刺组和药物组海马BDNF和CREB的表达较模型组上调(P<0.05).结论 针刺能改善抑郁症大鼠的行为学及海马神经元的病理变化,CREB-BDNF受体后信号转导通路是针刺抗抑郁的重要途径和作用靶点之一.     

白香丹胶囊配伍四逆散治疗焦虑大鼠的疗效及其对血清NE、5-HT、BDNF水平的影响

目的 探究白香丹胶囊配伍四逆散治疗焦虑大鼠的效果及其对血清去甲肾上腺素(NE)、5-羟色胺(5-HT)及脑源性神经营养因子(BDNF)水平的影响。方法 将48只大鼠随机分为空白组(正常饲养,10mL/kg纯水灌胃)、模型组(10mL/kg纯水灌胃)、四逆散组(四逆散水煎液3.6g/kg灌胃)、中药联合组(白香丹胶囊200mg/kg+四逆散水煎液3.6g/kg灌胃),造模、干预2周。采用旷场实验、高架十字迷宫(EPM)实验评估4组大鼠焦虑状态;酶联免疫吸附实验测定4组血清NE、5-HT及BDNF水平。结果 模型组旷场运动总距离长于空白组,中央区停留时间、开放臂进入次数比例(OE%)、开放臂停留时间比例(OT%)均低于空白组(P<0.05),中药联合组旷场运动总距离短于四逆散组(P<0.05),中央区停留时间、OE%、OT%高于四逆散组(P<0.05),且与空白组比较差异无统计学意义(P>0.05)。模型组大鼠血清NE、5-HT水平高于空白组(P<0.05),BDNF低于空白组(P<0.05);中药联合组血清NE、5-HT水平低于四逆散组(P<0.05),BDNF高于四逆散组(P<0.05),且与空白组比较差异无统计学意义(P>0.05)。结论 白香丹胶囊配伍四逆散治疗焦虑大鼠效果显著,其机制可能与上调BDNF表达和下调NE、5-HT水平有关。     

深低温体外循环对犬海马CA3区BDNF和CaBP表达的影响

目的研究深低温停循环时,不同脑保护方法对海马CA3区脑源性神经营养因子（BDNF）和钙结合蛋白（CaBP）表达的影响及意义。方法健康杂种犬18只,随机分为常温体外循环组（对照组）,深低温停循环组（DH-CA）,间断深低温停循环组（I-DHCA）,按临床方法建立体外循环。循环结束,取吻侧海马,经病理常规处理后,切片应用免疫组织化学染色方法观察海马CA3区BDNF和CaBP表达。结果DHCA组和I-DHCA组BDNF表达阳性细胞数多于对照组,差别有显著意义（P<0.01）,DHCA组表达显著多于I-DHCA组,差别有显著意义（P<0.01）。对照组和I-DHCA组CaBP蛋白表达阳性细胞数多于DHCA组,差别有显著意义（P<0.01）,对照组表达显著多于I-DHCA组,差别有显著意义（P<0.05）。结论I-DHCA脑保护效果优于DHCA,I-DHCA可以延长深低温停循环时限;BDNF和CaBP可能对减轻DHCA脑缺血缺氧损伤起重要作用。     

不同强度电针治疗对血管性痴呆大鼠学习记忆功能及海马CA1区β淀粉样蛋白1-40表达的影响

目的观测不同强度电针治疗对血管性痴呆大鼠学习记忆功能及海马CA1区β淀粉样蛋白1-40(Aβ1-40)表达的影响,寻求最佳电针治疗强度。方法共纳入60只雄性SPF级SD大鼠,采用随机数字表法随机选取8只大鼠为假手术组,其余大鼠采用改良的四血管阻断(4-VO)法复制VD模型,将造模成功的大鼠(24只)按随机数字表法完全随机分为模型组、1 m A电针组(频率2/15 Hz,强度1 m A,留针时间20 min)、3 m A电针组(频率2/15 Hz,强度3 m A,留针时间20 min),每组8只。电针组针刺百会、大椎穴,1次/d,连续治疗10 d,休息2 d为1个疗程。2个疗程后,采用Morris水迷宫试验检测各组大鼠学习记忆能力,运用荧光定量聚合酶链反应法检测大鼠海马CA1区Aβ1-40 m RNA表达水平。结果假手术组、模型组、1 m A电针组、3 m A电针组大鼠Morris水迷宫试验第2~5天平均逃避潜伏期分别为(46.8±1.9)、(40.6±2.3)、(24.6±1.5)、(19.4±1.2)s;(56.3±3.5)、(51.2±2.6)、(45.9±2.1)、(40.8±1.4)s;(52.7±1.5)、(46.0±2.3)、(31.3±1.2)、(27.7±1.6)s;(50.8±3.9)、(41.5±2.1)、(29.0±1.1)、(25.6±1.3)s;首次跨越原平台时间分别为(23.3±1.6)、(53.9±1.3)、(30.2±1.4)、(28.1±0.8)s,120 s内跨越原平台次数分别为(9.4±0.9)、(2.6±0.5)、(6.4±0.7)、(7.2±0.9)次;CA1区中Aβ1-40 mRNA表达水平分别为(17.3±1.1)、(40.7±1.1)、(24.0±1.7)、(22.4±1.8),组间差异均有统计学意义(F值分别为195.88、861.605、103.876、380.609,均P0.01);1 m A、3 m A电针组大鼠平均逃避潜伏期、首次跨越原平台时间较模型组明显缩短,120 s内跨越原平台次数较模型组明显增加,CA1区中Aβ1-40 mRNA表达水平较模型组明显降低,且3 m A电针组均明显优于1 m A电针组,差异均有统计学意义(均P0.05)。结论电针治疗可改善VD大鼠学习记忆能力并降低海马CA1区Aβ1-4 0 mRNA表达水平,3 m A电针效果优于1 m A电针。     

参芎化瘀胶囊对血管性痴呆大鼠海马CA1区BDNF表达的影响

目的探讨参芎化瘀胶囊对血管性痴呆（VD）模型大鼠海马CA1区脑源性神经营养因子（BDNF）表达的影响。方法将40只大鼠随机分为正常组、假手术组、模型组及参芎化瘀胶囊治疗组。采用反复夹闭双侧颈总动脉加腹腔注射硝普钠法,制备VD大鼠模型。应用Morris水迷宫试验检测VD大鼠的学习、记忆能力,HE染色观察大鼠海马CA1区神经元形态变化,免疫组化法检测BDNF表达。结果与正常组及假手术组比较,模型组出现明显学习、记忆障碍,海马区BDNF阳性细胞增多（P均〈0.01）;与模型组比较,治疗组学习记忆障碍明显改善、海马区BDNF阳性细胞增多（P〈0.05或〈0.01）。结论参芎化瘀胶囊能改善VD大鼠的学习、记忆能力,其机制可能与参芎化瘀胶囊上调BDNF表达有关。     

Bmal1通过肠嗜铬细胞及其TPH1-5-HT信号通路参与肠易激综合征的作用机制研究

背景：肠易激综合征(IBS)的发生与生物钟节律紊乱有关,IBS症状常具有昼夜波动等节律紊乱特征。肠嗜铬细胞(EC细胞)及其色氨酸羟化酶-1(TPH1)-5-羟色胺(5-HT)信号通路是目前公认的参与IBS发生的关键病理生理学机制。目的：探讨生物钟核心基因Bmal1是否通过调控EC细胞及其TPH1-5-HT信号通路参与IBS的发生。方法：采用IBS模型和对照Sprague-Dawley大鼠以及Bmal1肠道特异性敲除(Bmal1^△IEC)和野生型(WT)C57BL/6小鼠进行研究。以连续单一刺激方法建立IBS模型。以免疫荧光染色检测结肠Bmal1、EC细胞嗜铬粒蛋白A(Cg A)、TPH1和5-HT表达。结果：大鼠实验：Bmal1主要表达于结肠上皮细胞,在EC细胞中亦有表达。与对照组相比,授时因子时间点(ZT)ZT8:00和ZT24:00时,IBS模型组结肠Bmal1表达明显增高,且模型组ZT8:00的Bmal1表达明显高于ZT16:00和ZT24:00,差异均有统计学意义(P均<0.05)。小鼠实验：与WT组相比,Bmal1^△IEC组结...     

Electroacupuncture ameliorates learning and memory deficits via hippocampal 5-HT1A receptors and the PKA signaling pathway in rats with ischemic stroke

Metabolic Brain Disease - Hippocampal 5-HT1A receptors and the PKA signaling pathway have been implicated in learning and memory. This study aimed to investigate whether PKA signaling mediated by...     

电针对衰老模型大鼠学习记忆及海马CA1区LTP的影响

目的 研究电针对D-半乳糖致衰老大鼠学习记忆障碍和海马CA1区突触传递长时程增强(LTP)效应的影响,探索电针改善学习和记忆的作用机制.方法 将SD大鼠随机分为正常对照组、模型组和电针组.采用腹腔注射D-半乳糖的方法建立衰老大鼠模型;电针组选取百会和足三里穴给予大鼠电针治疗,参数设定为:3 Hz,1 mA,连续波.采用Morris水迷宫观察大鼠行为学变化;并采用高频刺激Schaffer侧支,然后在同侧海马CA1区诱导LTP的方法检测大鼠海马突触可塑性的变化.结果 模型组与正常对照组相比水迷宫测试中的逃避潜伏期明显延长,距离百分比明显降低(P＜0.05,P＜0.01);而电针组与模型组相比潜伏期明显缩短,距离百分比明显增大(P＜0.01).模型组与正常对照组相比海马CA1区LTP明显受到抑制(P＜0.01),而电针组能减轻D-半乳糖对海马CA1区LTP的抑制作用,明显改善突触功能的可塑性(P＜0.05).结论 电针可改善由D-半乳糖致衰老大鼠学习记忆能力,其作用机制之一可能与大鼠海马CA1区LTP的提高有关.     

Synaptic remodeling in hippocampal CA1 region of aged rats correlates with better memory performance in passive avoidance test

Aging is associated with deficits in long-term declarative memory formation, and wide differences in performance can be observed among aged individuals. The cellular substrates of these deficits and the reasons for such marked individual differences are not yet fully understood. In the present study, morphologic parameters of synapses and synaptic mitochondria in stratum molecolare of CA1 hippocampal region were investigated in aged (26- to 27-month-old) female rats after a single trial inhibitory avoidance task. In this memory protocol animals learn to avoid a dark compartment in which they received a mild, inescapable foot shock. Rats were tested 3 and 6 or 9 hours after the training, divided into good and bad responders according to their performance (retention times above or below 100 seconds, respectively) and immediately sacrificed. The number of synapses and synaptic mitochondria per cubic micrometer of tissue (numeric density), the average area of synapses and volume of synaptic mitochondria, the total area of synapses per cubic micrometer of tissue, the percentage of perforated synapses and the overall volume of mitochondria per cubic micrometer of tissue were evaluated. In the good responder group, the numeric density of synapses and mitochondria was significantly higher and the average mitochondrial volume was significantly smaller 9 hours versus 6 hours after the training. No significant differences were observed among bad responders. Thus, better performances in passive avoidance memory task are correlated with more efficient plastic remodeling of synaptic contacts and mitochondria in hippocampal CA1. Present findings indicate that maintenance of synaptic plastic reactivity during aging is a critical requirement for preserving long-term memory consolidation.     

Autoradiographic analyses of the effects of restraint-induced stress on 5-HT1A, 5-HT1C and 5-HT2 receptors in the dorsal hippocampus of male and female rats.

Quantitative autoradiography was used to evaluate the effects of sex and either 1 or 5 daily 2-hour sessions of restraint stress on binding at 5-HT1A, 5-HT1C and 5-HT2 receptors in the rat dorsal hippocampus. Neither sex nor restraint stress were found to have effects on binding at 5-HT1C or 5-HT2 receptors. However, restraint stress increased binding of [3H]8-hydroxy-2-(di-n-propylamino)tetralin at 5-HT1A receptors in the CA4 region and in the infrapyramidal dentate gyrus. In addition, levels of binding at 5-HT1A receptors in the oriens and lacunosum moleculare layers of the CA1 region were significantly higher in female rats. Neither estradiol benzoate nor estradiol benzoate plus progesterone had effects on binding at hippocampal 5-HT1A receptors in ovariectomized rats, making it unlikely that the sex differences were related to stages of the estrous cycle. Stress-induced levels of corticosterone (CORT) were higher in females. Although CORT levels in blood obtained during restraint decreased from session 1 to session 5 in both male and female rats, the decrease became significant in females only. Female rats also displayed higher levels of activity in the open field. Although activity in the open field was reduced in male and female rats after restraint, these decreases were not significant. Results are discussed in relation to anxiety and depression.     

间歇缺氧大鼠海马神经元凋亡及其机制

目的探讨间歇缺氧对大鼠海马组织氧化应激状态及海马神经元凋亡的影响及其可能的机制。方法将36只雄性Wistar大鼠随机分为间歇缺氧组、持续缺氧组和正常对照组，每组12只。采用化学比色法测定海马组织丙二醛和超氧化物歧化酶（SOD）水平，应用Western免疫印迹法检测海马CA1区磷酸化C—JUN氨基末端激酶（p-JNK）、磷酸化c-jun（p-c-jun）的表达水平，应用缺口末端标记（TUNEL）法检测海马CA1区神经元凋亡率。结果间歇缺氧组大鼠海马CAl区丙二醛水平为（1．61±0．39）nmol／mg蛋白，显著高于正常对照组的[（1．25±0．29）nmol／mg蛋白]和持续缺氧组的[（1．34±0．24）nmol／mg蛋白]；间歇缺氧组大鼠海马CAl区SOD水平为（45±13）NU／mg蛋白，显著低于正常对照组[（58±12）NU／mg蛋白]和持续缺氧组[（56±10）NU／mg蛋白]；持续缺氧组与正常对照组的差异均无统计学意义。间歇缺氧组p-JNK、p—c-jun表达显著增高，分别是正常对照组的2．1倍及2．3倍；间歇缺氧组海马CA1区神经元凋亡率为（0．30±0．16）％，显著高于正常对照组[（0．12±0．07）％]和持续缺氧组[（0．17±0．09）]。结论间歇缺氧可导致海马CA1区氧化应激状态，从而激活JNK信号传导通路，介导海马神经元凋亡，这可能是阻塞性睡眠呼吸暂停低通气综合征患者神经功能障碍的病理生理基础之一。【     

Effect of serotonin 5-HT1, 5-HT2, and 5-HT3 receptor antagonists on the prolactin response to restraint and ether stress.

Serotonin (5-HT) appears to be involved in the central control of the prolactin (PRL) response to suckling and estrogen. Furthermore, 5-HT may participate in the mediation of stress-induced PRL release. In order further to elucidate the role of 5-HT and the type of 5-HT receptor(s) involved in the PRL response to stress, we investigated the effect of blockade of 5-HT1, 5-HT2 or 5-HT3 receptors on the restraint or ether stress-induced release of PRL in male rats. Pretreatment with the 5-HT1 + 2 receptor antagonist methysergide (0.5 or 2.5 mg/kg i.p.) inhibited or prevented the PRL response to restraint or ether stress. Pretreatment with the 5-HT2 receptor antagonists ketanserin or LY 53857 (0.5 or 2.5 mg/kg i.p.) inhibited the response to restraint or ether stress approximately 30 or 60%, respectively. Higher doses of both 5-HT2 receptor antagonists (10 mg/kg i.p.) had a minor inhibitory effect (5-30% for ketanserin and 50% for LY 53857). Prior intraperitoneal administration of the 5-HT3 receptor antagonists ICS 205-930 or GR 38032F (0.05-2.5 mg/kg i.p.) inhibited the restraint stress-induced PRL release dose-dependently. Both compounds inhibited the PRL response to ether stress, but only the effect of GR was dose-related. The maximal inhibitory effect (70% inhibition of the PRL response to restraint or ether stress) was obtained for both compounds at a dose of 0.1 mg/kg. We conclude that serotonergic neurons are involved in the mediation of the stress-induced PRL release by activation of 5-HT1, 5-HT2 as well as 5-HT3 receptors.     

Local generation of multineuronal spike sequences in the hippocampal CA1 region

Sequential activity of multineuronal spiking can be observed during theta and high-frequency ripple oscillations in the hippocampal CA1 region and is linked to experience, but the mechanisms underlying such sequences are unknown. We compared multineuronal spiking during theta oscillations, spontaneous ripples, and focal optically induced high-frequency oscillations (“synthetic” ripples) in freely moving mice. Firing rates and rate modulations of individual neurons, and multineuronal sequences of pyramidal cell and interneuron spiking, were correlated during theta oscillations, spontaneous ripples, and synthetic ripples. Interneuron spiking was crucial for sequence consistency. These results suggest that participation of single neurons and their sequential order in population events are not strictly determined by extrinsic inputs but also influenced by local-circuit properties, including synapses between local neurons and single-neuron biophysics.A hypothesized hallmark of cognition is self-organized sequential activation of neuronal assemblies (1). Self-organized neuronal sequences have been observed in several cortical structures (2–5) and neuronal models (6–7). In the hippocampus, sequential activity of place cells (8) may be induced by external landmarks perceived by the animal during spatial navigation (9) and conveyed to CA1 by the upstream CA3 region or layer 3 of the entorhinal cortex (10). Internally generated sequences have been also described in CA1 during theta oscillations in memory tasks (4, 11), raising the possibility that a given neuronal substrate is responsible for generating sequences at multiple time scales. The extensive recurrent excitatory collateral system of the CA3 region has been postulated to be critical in this process (4, 7, 12, 13).The sequential activity of place cells is “replayed” during sharp waves (SPW) in a temporally compressed form compared with rate modulation of place cells (14–20) and may arise from the CA3 recurrent excitatory networks during immobility and slow wave sleep. The SPW-related convergent depolarization of CA1 neurons gives rise to a local, fast oscillatory event in the CA1 region (“ripple,” 140–180 Hz; refs. 8 and 21). Selective elimination of ripples during or after learning impairs memory performance (22–24), suggesting that SPW ripple-related replay assists memory consolidation (12, 13). Although the local origin of the ripple oscillations is well demonstrated (25, 26), it has been tacitly assumed that the ripple-associated, sequentially ordered firing of CA1 neurons is synaptically driven by the upstream CA3 cell assemblies (12, 15), largely because excitatory recurrent collaterals in the CA1 region are sparse (27). However, sequential activity may also emerge by local mechanisms, patterned by the different biophysical properties of CA1 pyramidal cells and their interactions with local interneurons, which discharge at different times during a ripple (28–30). A putative function of the rich variety of interneurons is temporal organization of principal cell spiking (29–32). We tested the “local-circuit” hypothesis by comparing the probability of participation and sequential firing of CA1 neurons during theta oscillations, natural spontaneous ripple events, and “synthetic” ripples induced by local optogenetic activation of pyramidal neurons.     

抗细胞间黏附分子-1单抗对心肌缺血再灌注早期和远期心功能的影响

目的　研究抗细胞间黏附分子 1(ICAM 1)单抗对大鼠心肌缺血再灌注早期和远期死亡率及心功能的影响。方法　应用大鼠心肌缺血再灌注 2 4h和再灌注 6周模型。以氯化 2 ,3,5 三苯基四氮唑 (TTC)染色法确定心肌坏死范围。血流动力学分析系统测定平均动脉压、左心室收缩期压力峰值 (LVSP)、左心室舒张末期压 (LVEDP)、左心室最大上升速度 (+Pmax)和下降速度 (-Pmax)等指标。结果　用药组大鼠缺血 4 5min再灌注 2 4h ,与对照组相比死亡率差异无显著性意义 (P >0 .0 5 ) ,心肌梗死范围缩小 ,与对照组比较差异有显著性意义 (P <0 .0 5 ) ,LVSP ,+Pmax ,收缩功能 [L(1+2 ) ]、-Pmax、舒张功能 [L(3+4) ]与对照组比较差异有显著性意义 (P <0 .0 5 )。再灌注 6周用药组和对照组间死亡率差异有显著性意义 (P <0 .0 5 )。LVSP ,+Pmax和L(1+2 )与对照组比较差异有显著性意义 (P <0 .0 5 )。而LVEDP ,-Pmax、L(3+4)与对照组比较差异无显著性意义 (P >0 .0 5 )。结论　抗ICAM 1单抗对大鼠心肌缺血再灌注早期和远期心功能均有保护作用     

老年大鼠海马细胞凋亡和神经元信号转导通路的变化与学习记忆的关系

目的 研究海马细胞凋亡、神经元信号转导通路在老年大鼠大脑中的变化及其与学习记忆的关系.方法 选用8月龄和24月龄大鼠,利用Y迷宫测定大鼠学习记忆能力;TUNEL法检测其海马区神经元凋亡;免疫组织化学染色和SDS聚丙烯酰胺凝胶转移电泳检测PI3K、p-PI3K、AKt、p-AKt和Caspase-9p35的表达水平.结果 老年大鼠与青年鼠相比,学习尝试次数明显增加,记忆正确次数明显减少;海马区可见到较多TUNEL阳性神经元;p-PI3K和p-AKt的活性明显降低,Caspase-9 p35的表达明显增加;P13K和AKt的表达在两组之间没有明显变化.结论 老年大鼠学习记忆能力下降与海马细胞凋亡及PI3K-AKt-Caspase-9信号转导通路的障碍有关.     

长期应用不同剂量左旋多巴对帕金森病大鼠模型学习记忆能力和血浆同型半胱氨酸的影响

目的 观察长期应用不同剂量左旋多巴(L-dopa)对帕金森病(PD)模型大鼠的学习记忆能力和血浆同型半胱氨酸(Hcy)的影响.方法 应用6-羟多巴胺(6-OHDA)制作PD大鼠模型.将288只成功PD模型大鼠分为对照组及实验组.实验组再分为3个不同剂量组,分别用不同剂量的L-dopa腹腔注射(10 mg/kg/d,20 mg/kg/d,30 mg/ kg/d)连续28 d,分别于不同时点(1、3、5、7、14和28 d)作行为学测定,并抽血测定Hcy、叶酸;同时分离大鼠海马区制作冰冻切片,进行刚果红染色并测定海马区β淀粉样蛋白阳性斑块的积分吸光度.结果 随着应用L-dopa剂量的增大、时间的增加可使PD模型大鼠学习记忆能力明显下降(P<0.05);海马区β淀粉样蛋白阳性斑块增多(P<0.05).血浆Hcy浓度变化不一,随L-dopa剂量增大而升高,随L-dopa应用时间增长而波动,叶酸浓度降低(P<0.05).结论 长期大量使用L-dopa能使PD模型大鼠学习记忆能力明显下降,血浆Hcy浓度升高,引起β淀粉样蛋白阳性斑块增多,推测PD痴呆(PDD)可能与Hcy升高有关.