氯胺酮对抑郁大鼠前额皮层及海马IL-1β和IL-6表达的影响

目的 检测抑郁大鼠给予氯胺酮后,前额皮层及海马区组织内IL-1β和IL-6表达的变化.方法 Wistar大鼠雄性20只按照随机方式分为2组,各10只,给予生理盐水的大鼠入对照组（C组）,给予10 mg/kg氯胺酮的大鼠为K组.应用行强迫游泳实验15 min的方法建立大鼠抑郁模型.次日,腹腔注射氯胺酮或等体积生理盐水,注射30 min后再次进行强迫游泳实验5 min,记录不动时间.并分别采用Western Blot法和双抗体夹心ABC-ELISA法检测大鼠前额皮层及海马组织中IL-1β和IL 6的表达情况.结果 与对照组比较,应用氯胺酮后大鼠强迫游泳不动时间明显减少（P＜0.01）,大鼠前额皮层及海马区的IL-1β和IIL-6表达均明显下调（P＜0.05）.结论 氯胺酮对抑郁大鼠的抗抑郁作用可能与前额皮层及海马IL-1和IL-6的表达下调有关.     

MK-801建立谷氨酸功能低下精神分裂症大鼠模型的研究

目的 用N-甲基-D-天门冬氨酸(NMDA)非竞争性受体拮抗剂地卓西平马来酸盐(MK801)建立具有类精神分裂症症状的大鼠模型.方法 24只SD大鼠随机分为MK801组、生理盐水组和正常对照组,每组各8只.MK801组的大鼠每天腹膜腔内注射0.5 mg/kg(给药体积为10 mL/kg)MK801共6 d以建立精神分裂症模型,生理盐水组给予等体积生理盐水.用自发活动、强迫游泳试验、逃避性抑制(inhibitory avoidance,IA)试验以及海马神经生长因子表达评价该模型.结果 MK801组、生理盐水组和对照组的大鼠10min自发活动总路程分别为(3127±381)cm、(935±196)cm、(1060±243)cm,游泳不动时间分别为(147±18)s、(58±10)s、(52±10)s.3组的自发活动和游泳不动时间差异均有统计学意义(F=149.7,P<0.01;F=122.6,P<0.01),MK801组的自发活动较另两个组均增加(P<0.01),而游泳不动时间延长(P<0.01).3组的24 h IA的记忆潜伏期也有明显差异(F=5.2,P<0.05),MK801组的记忆潜伏期[(26±10)s]较生理盐水组[(47±16)s]和对照组[(46±14)s]均缩短(P<0.05).而且,MK801组海马神经生长因子表达明显下调.结论 连续给予高剂量MK801诱导的大鼠谷氨酸功能低下模型不仅具有类精神分裂症症状.而且还存在神经生物学改变,可作为模拟精神分裂症的模型.     

内源性大麻素对海马神经元AMPA受体GluR2的作用

目的探索内源性大麻素预处理对小鼠全脑缺血再灌注损伤后海马神经元α-氨基-3羟基-5-甲基-4-异恶唑丙酸(AMPA)受体2亚基(GluR2)表达的影响及机制。方法雄性C57BL/6小鼠随机分为假手术组、模型组、2-花生酰基甘油(2-AG)处理组、大麻素1型受体(CB1R)拮抗剂(AM251)+2-AG组和溶剂组。2-AG处理组腹腔注射2-AG 5 mg/kg;AM251+2-AG组腹腔注射AM251 1 mg/kg,30 min后腹腔给予2-AG 5 mg/kg;溶剂组腹腔给予0.1 ml二甲基亚砜(DMSO)。各组小鼠在预处理后30 min采用夹闭双侧颈总动脉20 min行再灌注的方法制备全脑缺血再灌注损伤模型。再灌注2 h取材行Western blot及免疫荧光检测。结果 GluR2高表达于正常小鼠海马CA1区锥体神经元;C57小鼠全脑缺血20 min,再灌后2 h海马组织GluR2表达明显下调(P0.05);与模型组比较,2-AG处理组海马组织GluR2明显增高(P0.05);与2-AG处理组比较,AM251+2-AG组海马组织GluR2明显下降(P0.05)。结论内源性大麻素2-AG作用于神经元CB1R,逆转全脑缺血损伤导致的海马神经元GluR2表达下降。     

地卓西平马来酸盐对抑郁大鼠行为学和前额叶BDNF表达的影响

目的观察地卓西平马来酸盐(MK-801)预处理对利血平诱导的抑郁模型大鼠抑郁行为的改善作用及大脑前额叶脑源性神经营养因子(BDNF)表达的影响。方法采用随机数字表法将32只成年雄性SD大鼠分为4组:对照组、利血平模型组、MK-801+利血平组和MK-801组,每组8只。MK-801+利血平组和MK-801组预先给予腹腔注射MK-801(0.3 mg/kg),对照组和利血平模型组腹腔注射相应体积的生理盐水。30 min后,利血平模型组和MK-801+利血平组腹腔注射利血平(4 mg/kg),对照组和MK-801组腹腔注射相同体积的乙酸溶剂。注射利血平48 h后利用强迫游泳实验观察大鼠的抑郁样行为表现,并在行为实验完成后处死大鼠,以酶联免疫吸附实验(ELISA)检测大脑前额叶BDNF的表达水平。结果在强迫游泳实验中,利血平模型组强迫游泳不动时间[(49.38±7.85)s]长于对照组[(15.59±5.43)s],差异有统计学意义(t=11.91,P0.01);MK-801+利血平组强迫游泳不动时间[(12.32±4.25)s]短于利血平模型组,差异有统计学意义(t=13.06,P0.05)。ELISA结果显示,利血平模型组前额叶BDNF表达水平[(10.09±0.88)ng/mL]低于对照组[(13.29±1.10)ng/mL],差异有统计学意义(t=6.44,P0.01);MK-801+利血平组大鼠前额叶的BDNF表达水平[(12.56±1.83)ng/mL]高于利血平模型组,差异有统计学意义(t=3.44,P0.05)。结论 MK-801可改善大鼠的抑郁样行为,其机制可能与调节脑内BDNF的表达有关。     

ω-3多不饱和脂肪酸对老年痴呆大鼠学习记忆和海马MDA、SOD的影响

目的 探讨ω-3多不饱和脂肪酸治疗老年痴呆的可能机制.方法 将15月龄健康雌性Wistar大鼠随机分为对照组、痴呆模型组和ω-3多不饱和脂肪酸治疗组[按体质量2.5 g/(kg·d)给予二十碳五烯酸灌胃,共6周],观察大鼠跳台潜伏时间及错误次数,同时测定大鼠海马组织总SOD活力和MDA含量.结果 与痴呆模型组比较,ω-3多不饱和脂肪酸治疗组大鼠的跳台潜伏时间明显延长[分别为(230.88±29.35)s 与 (189.26±31.42)s](P<0.01),触电错误次数减少[分别为(7.3±2.2)次与(9.6±2.2)次](P<0.05),同时其大鼠海马组织总SOD活力增加[分别为(70.19±12.85) U/mg prot与(50.47±14.99) U/mg prot]和MDA含量减少[分别为(7.77±1.57)nmol/mg prot与(9.39±1.44) nmol/mg prot](P<0.05).结论 ω-3多不饱和脂肪酸可改善大鼠学习记忆能力,保护脑组织免遭自由基攻击,在一定程度上为临床治疗老年痴呆提供了实验基础.     

重复经颅磁刺激通过调节海马的核因子转录因子抗氧化信号通路改善慢性不可预见应激大鼠的抑郁样行为北大核心CSCD

目的探讨重复经颅磁刺激(rTMS)对慢性不可预见应激(CUS)大鼠抑郁行为及海马区核因子转录因子(Nrf2)抗氧化基因表达的影响。方法将24只SD雄性大鼠按安全随机法分为对照组、CUS组、CUS+rTMS组,每组各8只。适应性饲养7 d后,CUS组、CUS+rTMS组大鼠给予CUS刺激,然后给予CUS+rTMS组大鼠5 Hz的rTMS刺激干预7 d,其他组接受假刺激。最后一次rTMS干预结束24 h后进行糖水偏好、旷场和强迫游泳测试,随后处死动物,通过实时定量PCR(RT-PCR)和蛋白免疫印迹法检测海马的Nrf2、血红素加氧酶1(HO-1)和超氧化物歧化酶1(SOD-1)的表达变化。将另外24只大鼠按安全随机法分为3组:对照病毒+CUS组、对照病毒+CUS+rTMS组、Nrf2下调病毒(shNrf2)+CUS+rTMS组,每组各8只;对照病毒+CUS组、对照病毒+CUS+rTMS组大鼠海马注射对照病毒,shNrf2+CUS+rTMS组大鼠海马注射shNrf2。注射病毒2周后,均接受CUS刺激,然后给予rTMS(5 Hz)或假刺激干预7 d。干预结束24 h后进行行为学及分子生物学检测。结果(1)与对照组相比,CUS组大鼠糖水偏好减少[(39.33±11.85)%比(77.31±4.69)%;F=8.32,P<0.01],旷场中心活动时间减少[(14.70±4.27)s比(52.49±1.07)s;F=3.84,P<0.05)],强迫游泳不动时间增加[(38.70±4.27)s比(24.19±1.07)s;F=10.31,P<0.01)],海马Nrf2、HO-1和SOD-1表达下调(P<0.05);(2)与CUS组相比,CUS+rTMS组大鼠的糖水偏好和旷场中心活动时间增加(均P<0.05),强迫游泳不动时间减少(P<0.05),海马Nrf2、HO-1和SOD-1表达上调(P<0.05)。(3)与对照病毒+CUS+rTMS组相比,shNrf2+CUS+rTMS组大鼠海马Nrf2及下游靶基因HO-1和SOD-1表达下调(P<0.05),大鼠的糖水偏好和旷场中心活动时间减少(均P<0.05),强迫游泳不动时间增加(P<0.05)。结论 rTMS通过调节CUS大鼠海马Nrf2及其下游分子HO-1和SOD-1表达而缓解CUS大鼠的抑郁行为,发挥抗抑郁效果。     

补骨脂素抗抑郁作用及机制研究

目的 研究补骨脂素的抗抑郁作用及机制。方法 采用大鼠强迫游泳、小鼠强迫游泳及 小鼠悬尾3 种抑郁模型，将动物随机分为对照组、补骨脂素低剂量组、补骨脂素高剂量组、阿米替林组， 观察各组药物对大/ 小鼠强迫游泳不动时间和悬尾不动时间的影响；同时在细胞水平建立皮质酮损伤 PC12 细胞模型，观察补骨脂素的细胞保护作用。结果 在大/ 小鼠强迫游泳和小鼠悬尾实验中，补骨 脂素可显著缩短大/ 小鼠的强迫游泳不动时间和悬尾不动时间，与对照组比较差异均有统计学意义 （P＜ 0.05）；皮质酮损伤PC12 细胞模型中，补骨脂素显著提高 PC12 细胞的存活率，拮抗皮质酮诱导的细 胞损伤作用。结论 补骨脂素具有抗抑郁效应，其机制可能与神经细胞保护作用相关。     

小檗碱对癫痫大鼠脑组织P-糖蛋白表达的影响

目的 探讨小檗碱(BBR)对癫痫大鼠脑组织P-糖蛋白(P-gp)表达的影响.方法 将44只SD大鼠随机分为假手术组(9只)、癫痫组(9只)和BBR 10 mg/kg(9只)、20 mg/kg(9只)、40 mg/kg组(9只).采用大鼠海马注射海人酸方法制作癫痫模型,各BBR干预组分别于术前48 h、术前24h和术后6h腹腔注射相应剂量BBR.观察各组大鼠癫痫发作潜伏期及发作严重程度.造模24 h后,采用免疫组化方法检测并比较各组大鼠海马CA3区P-gp和核因子-κB(NF-κB) p65的表达水平.结果 BBR 20 mg/kg组[(66.11±5.90) min,(26.67±6.67) min]和40 mg/kg组[(76.33±9.11) min,(42.00±7.73) min]大鼠癫痫发作潜伏期及初次至第6次≥Ⅳ级痫样发作间隔时间均明显长于癫痫组[(41.78±10.45) min,(9.44±4.25)min](均P＜0.05).各组大鼠海马CA3区NF-κB p65和P-gp表达的差异均有统计学意义(H=16.024,H=21.830;均P＜0.01).癫痫组海马CA3区NF-κB p65和P-gp表达显著高于假手术组(均P＜0.05);BBR 20mg/kg和40 mg/kg组表达显著低于癫痫组(均P＜0.05).结论 BBR能够延长癫痫发作潜伏期、降低其严重程度,并抑制癫痫大鼠脑组织NF-κB和P-gp的表达.     

强迫性游泳压力对大鼠单胺水平和神经退行性变化没有影响(英文)

目的本文旨在研究强迫性游泳试验中的不动时间(压力的行为性指示)与海马中单胺水平(抑郁指标)、血浆中肾上腺素水平(循环系统中的压力指标)以及神经退行性变化(fluoro-jade C染色法检测)的关系。方法给予雄性Sprague-Dawley大鼠急性、亚慢性(7天)或慢性(14天)强迫游泳的压力,并在强迫游泳试验中记录大鼠的不动时间。试验结束后,用高效液相色谱电化学检测法测定大鼠海马中去甲肾上腺素、5-羟色胺和多巴胺以及血浆中肾上腺素的水平,并对大鼠脑片进行fluoro-jade C染色。结果急性、亚慢性和慢性压力的大鼠均显示出较长的不动时间,分别为(214±5)s,(220±4)s和(231±7)s,表明这些大鼠都处在压力状态下。然而,与非压力状态下的对照组大鼠相比,急性和亚慢性压力下的大鼠海马中单胺类分子的水平并没有显著降低,并且血浆中肾上腺素的水平也没有显著升高。此外,慢性压力大鼠的脑片呈现出fluoro-jade C染色阴性。结论强迫性游泳试验中的不动时间与抑郁和压力并不相关,提示此法可能不能准确地指示压力水平。     

莲心碱对抑郁症模型小鼠的抗抑郁作用

目的：观察莲心碱对抑郁症模型小鼠的抗抑郁活性。方法将 ICR 小鼠按随机数字表分为溶剂对照组、盐酸氟西汀组（10 mg／kg）、莲心碱组（5,10,20 mg ／kg）。采用小鼠悬尾实验、小鼠强迫游泳实验两个经典行为绝望模型,探讨莲心碱的抗抑郁作用;并采用开场实验观察莲心碱有无中枢神经兴奋作用。结果在悬尾实验和强迫游泳实验中,与溶剂对照组相比,不同剂量的莲心碱均能显著缩短小鼠悬尾不动时间和强迫游泳不动时间,且在开场实验中对小鼠自发活动无明显影响。结论莲心碱具有一定的抗抑郁活性,且无中枢神经兴奋作用。     

Diurnal variation in the concentrations of catecholamines and indoleamines in the median eminence and in the intermediate and posterior lobes of the pituitary gland of the male rat

Diurnal changes in monoamine concentrations were studied in the median eminence and in the intermediate and posterior lobes of the pituitary gland of the male rat. The concentrations of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), noradrenaline (NA) and dopamine (DA) were analyzed at 7 time points over a 24-h period. Diurnal variation was analyzed by analysis of variance (ANOVA) with time of day as a class variable as well as by 24 h and 12 h cosine curve fittings. There were marked time-dependent changes in the median eminence concentrations of 5-HT (ANOVA: P = 0.0085), 5-HIAA (P = 0.003) and NA (P = 0.0003). Cosine curves with 24-h periods fit the data points with peaks around 13.00 h. DA levels also varied with an apparent 24-h rhythm in the median eminence, but the changes did not reach the level of significance in the ANOVA. In the intermediate lobe of the pituitary gland, the concentrations of DA varied significantly during the course of the 24-h cycle (P = 0.0011) and were well-fitted to a 24-h cosine wave. The 5-HIAA levels also showed marked diurnal changes (P = 0.025) with an evident 12-h rhythm. In contrast, NA and 5-HT concentrations did not appear to vary during the 24-h cycle. In the posterior lobe of the pituitary gland. DA had a 24-h rhythm (P = 0.0005) similar to the intermediate lobe. NA and indoleamine levels did not show any significant variation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrophysiology and analysis of the image of the development of Purkinje cells in culture and in the intact animal

The electrophysiological and morphological properties of the Purkinje cells (P cells) grown in organotypic cultures were studied in HRP intracellulary labelled neurons and compared to Golgi stained P cells from kitten of different ages. The effects of afferent fiber depletions on the final dendritic topological parameters were investigated by 3-dimensional reconstructions and computerized methods. In culture, the P cell dendritic trees always appeared reduced in size when compared to their in vivo counterparts. A discriminant analysis permitted the recognition of 3 populations of cultured P cells according to the type of deafferentation. In intact animals, the dendritic organization appeared biplanar around day 13. These results demonstrate that the presence of all normal inputs is required to achieve the full elaboration and the monoplanar disposition of the P cell dendrites.     

Fighting in the aged male mouse increases the expression of TrkA and TrkB in the subventricular zone and in the hippocampus

In the present study, we investigate the effect of aggressive behavior and release of nerve growth factor (NGF) on brain progenitor cells. We found that the condition of subordination enhances the level of NGF in the subventricular zone and hippocampus whereas dominance elevates brain derived neurotrophic factor (BDNF). It was also found that mRNA-TrkA is over-expressed in the subventricular zone and hippocampus of dominant and subordinate mice, whereas mRNA-TrkB is increased in the subventricular zone of both dominants and subordinates and in the hippocampus of dominant mice. Fighting was also associated with increased presence of proliferating cells in the hippocampus stained with the nuclear marker bromodeoxyuridine (BrdU). Moreover, the brain of subordinate mice displayed tyrosine hydroxylase (TH) immunoreactivity in the wall of the periventricular region of the third ventricles and a marked neuropeptide Y (NPY) presence in the hippocampus co-expressed with BrdU. These results provide additional evidence that agonistic behavior in the aged mouse alters neurotrophin levels and increases brain progenitor cells number. The functional significance of these findings is discussed.     

Imaging and modelling of digestion in the stomach and the duodenum

Gastroduodenal physiology is traditionally understood in terms of motor-secretory functions and their electrical, neural and hormonal controls. In contrast, the fluid-mechanical functions that retain and disperse particles, expose substrate to enzymes, or replenish the epithelial boundary with nutrients are little studied. Current ultrasound and magnetic resonance imaging allows to visualize processes critical to digestion like mixing, dilution, swelling, dispersion and elution. Methodological advances in fluid mechanics allow to numerically analyse the forces promoting digestion. Pressure and flow fields, the shear stresses dispersing particles or the effectiveness of bolus mixing can be computed using information on boundary movements and on the luminal contents. These technological advances promise many additional insights into the mechanical processes that promote digestion and absorption.