慢性应激对心肌梗死后大鼠模型行为学及海马BDNF的影响

目的:探讨慢性应激对心肌梗死后大鼠模型行为学及海马BDNF的影响.方法:建立急性心肌梗死模型.结合慢性不可预见的轻度应激和孤养制作心梗并抑郁复合大鼠模型.观察动物的体重变化和行为学指标,用Westernblot方法检测海马BDNF蛋白表达.结果:经过21天慢性不可预见轻度应激.模型组大鼠体重、糖水消耗和糖水偏爱百分比、敞箱试验得分均明显降低,纯水消耗显著增加;海马BDNF蛋白表达减少(P<0.05).结论:对急性心肌梗死大鼠采用21天慢性应激后,模型鼠体重下降、行为学明显异常,符合抑郁动物的行为学改变,且存在海马神经元可塑性降低的表现,这可能是心肌梗死并抑郁发病的机制之一.     

足底电击应激对小鼠脑组织神经递质水平变化的影响

目的:分析足底电击应激对小鼠前额叶皮层、海马、杏仁核神经递质的影响。方法:选择健康雌性成年C57BL/6J小鼠,随机分为对照组和足底电击应激组。应激组给予不可逃避足底电击,隔日1次,持续14d。足底电击应激结束次日进行糖水偏爱实验评估小鼠抑郁样行为;提取小鼠前额叶皮层、海马、杏仁核,试剂盒检测谷氨酸和γ-氨基丁酸(GABA)含量,高效液相色谱方法检测去甲肾上腺素(NE)和5-羟色胺(5-HT)含量。结果:与对照组相比,足底电击应激小鼠糖水偏爱指数明显降低;足底电击应激小鼠杏仁核谷氨酸水平显著升高、前额叶皮层及海马GABA水平显著下降;前额叶皮层、海马谷氨酸及杏仁核GABA表达水平无显著差异;足底电击应激小鼠前额叶皮层5-HT、杏仁核NE水平显著升高;前额叶皮层、海马NE,以及海马、杏仁核5-HT表达水平无显著差异。结论:足底电击应激引起小鼠抑郁样行为,上调杏仁核谷氨酸、NE以及前额叶皮层5-HT的表达,下调前额叶皮层、海马GABA的表达。     

解郁丸对WKY大鼠的抑郁样行为及海马和前额叶皮层BDNF表达的影响

目的:观察解郁丸对Wistar-Kyoto(WKY)大鼠抑郁样行为及脑源性神经营养因子(BDNF)在海马和前额叶皮层表达的影响,探讨其抗抑郁作用及相关机制。方法:成年雄性WKY大鼠为内源性抑郁动物模型,选取同品系Wistar大鼠作为空白对照组,WKY大鼠随机分为模型组、西酞普兰组和解郁丸组,分别灌胃给药21 d后,用糖水偏好实验及强迫游泳实验观察各组大鼠抑郁行为变化;采用免疫荧光法和Western blot法检测海马及前额叶皮层BDNF表达水平的变化。结果:WKY大鼠表现出明显的抑郁样行为,海马及前额叶皮层的BDNF表达量显著下降,且海马区神经元轴突减少(P0.01);在药物治疗后,WKY大鼠的抑郁样行为明显减少,BDNF在海马及前额叶皮层中的表达增加,且轴突数目也增加(P0.01)。结论:解郁丸能有效减少WKY大鼠的抑郁样行为;BDNF是其抗抑郁作用发挥的关键因子。本研究也进一步验证BDNF参与抑郁的发生发展过程。     

槲皮素治疗联合运动训练对脑卒中后大鼠抑郁样行为影响的研究

目的:探讨槲皮素治疗联合运动训练对脑卒中模型大鼠抑郁样行为的治疗作用。方法:将50只大鼠随机分为假手术组(sham)、卒中抑郁组(PSD)、槲皮素组(QUE)、运动组(EXE)和槲皮素+运动组(QUE+EXE)。通过大脑中动脉闭塞(MCAO)技术制备大鼠卒中后抑郁模型。通过悬尾实验(TST)和糖水偏爱实验(SPT)来评估各组大鼠抑郁样行为;利用酶联免疫吸附试验(ELISA)检测各组大鼠血清和前额叶皮质中肿瘤坏死因子α(TNF-a)和白细胞介素1-β(IL-1β)的含量;利用Western Blot检测各组大鼠前额叶皮质中脑源性神经生长因子(BDNF)、原肌球蛋白受体激酶B (Trk-B)、糖原合成酶激酶-3β(GSK-3β)和β-连环蛋白(β-catenin)的表达。结果:行为学检测结果显示PSD组大鼠不动的时间显著增加(P<0.05),同时糖水摄入量及糖水偏爱百分比均显著下降(P<0.05),而槲皮素和运动训练均逆转了这些行为(P<0.05)。ELISA检测显示PSD组大鼠血清及前额叶皮质中TNF-α和IL-1β表达升高(P<0.05),而槲皮素和运动训练均不...     

慢性应激抑郁模型大鼠海马Trek-1、GFAP表达情况及氟西汀的干预作用

目的:研究慢性不可预知性应激(Chronic Unpredictable Stress,CUS)诱导的抑郁大鼠海马新型双孔钾离子通道亚单元Trek-1及胶质纤维酸性蛋白(Glial Fiber Acidic Protein,GFAP)的表达变化以及氟西汀的干预作用。方法:成年SD大鼠48只,随机选取12只为正常对照组,其余采用慢性不可预知性应激建立慢性应激抑郁模型。21d后随机分为CUS组、氟西汀低剂量组,氟西汀高剂量组;采用糖水偏爱实验、旷场试验评定大鼠抑郁水平;采用荧光实时定量聚合酶链反应测定大鼠海马Trek-1、GFAPm RNA表达,TUNEL染色观察海马神经元凋亡。结果:造模后,CUS组、氟西汀低、高剂量组糖水消耗、糖水偏爱、垂直运动次数和水平运动次数明显低于对照组;干预后,CUS组以上指标明显低于对照组,氟西汀低、高剂量组经治疗后以上指标高于CUS组及干预前,但仍低于对照组。CUS组细胞凋亡率、Trek-1m RNA表达显著升高,GFAPm RNA表达下降,较对照组相比有统计学意义;氟西汀低、高剂量组海马CA1区细胞凋亡率、Trek-1m RNA表达下降,GFAPm RNA表达升高,与CUS组相比有统计学意义。结论:氟西汀可能通过改变海马Trek-1、GFAP表达,抑制细胞凋亡改善CUS大鼠抑郁症状。     

褪黑素抑制可卡因诱导的条件性位置偏爱大鼠DNMT1的下调

目的研究褪黑素拮抗大鼠可卡因诱导的条件性位置偏爱的作用和可能机制。方法建立可卡因诱导的条件性位置偏爱模型,诱导前30min给予褪黑素腹腔注射,检测实验大鼠条件性位置偏爱的变化,并应用Western blot、免疫荧光共聚焦激光扫描显微镜及real-time PCR技术,检测褪黑素对大鼠前额叶皮层中可卡因诱导的DMNT1表达的影响。结果褪黑素对可卡因诱导的大鼠条件性位置偏爱效应具有显著的抑制作用。共聚焦显微镜和Western blot结果表明,可卡因诱导大鼠前额叶皮层中DNMT1表达的减少,而褪黑素能够抑制可卡因的这种作用。Real-time PCR检测结果证明,可卡因诱导大鼠前额叶皮层中DNMT1 mRNA的下调,而褪黑素能够抑制这种作用。结论褪黑素可能通过抑制大鼠前额叶皮层中DNMT1表达的下调拮抗可卡因诱导的条件性位置偏爱。     

米诺环素对CCI大鼠抑郁样行为的影响及机制研究

目的:观察海马CA1区注射米诺环素对坐骨神经慢性缩窄性损伤(CCI)大鼠的抑郁样行为、海马和前额叶皮层小胶质细胞激活的影响并分析其机制。方法:成年SD雄性大鼠随机分为:对照组、假手术组、CCI模型组、CCI+米诺环素组。糖水偏好及旷场实验检测大鼠抑郁样行为;免疫组化观察海马以及前额叶皮层Iba-1表达;取海马以及前额叶皮层组织,real-time PCR观察Iba-1、NLRP3和caspase1 mRNA表达,ELISA测定IL-1β和IL-18含量。结果:与假手术组相比,CCI大鼠7、10 d和14 d的糖水偏好明显降低(P 0. 05),旷场中央活动距离和中央活动时间明显减少(P 0. 05);与CCI组相比,CA1区注射米诺环素后CCI大鼠7 d和14 d的糖水偏好明显升高(P 0. 05),旷场中央活动距离和中央活动时间明显增加(P 0. 05)。与假手术组相比,CCI组大鼠海马CA1、CA3及DG区和前额叶皮层Iba-1阳性细胞数目显著增多(P 0. 05),Iba-1、NLRP3和caspase1 mRNA表达明显上调; IL-1β和IL-18含量也明显升高(P 0. 05)。与CCI组相比,注射米诺环素后,CCI大鼠海马CA1、CA3及DG区和前额叶皮层Iba-1阳性细胞数目减少(P 0. 05),Iba-1、NLRP3和caspase1 mRNA表达降低(P 0. 05),IL-1β和IL-18含量降低(P 0. 05)。结论:海马CA1区注射米诺环素明显抑制CCI大鼠的抑郁样行为;其机制可能是抑制海马和前额叶皮层小胶质细胞激活,下调NLRP3和caspase1表达,从而使IL-1β和IL-18产生减少。     

毛蕊花糖苷对抑郁症大鼠行为学和前额叶皮层内质网应激的影响

目的:观察毛蕊花糖苷(acteoside)对抑郁症大鼠行为学及前额叶皮层内质网应激(endoplasmic reticulum stress,ERS)的影响,探讨毛蕊花糖苷的抗抑郁机制。方法:将108只健康雄性SD大鼠按照随机数字表法分为对照组、模型组、阳性对照氟西汀(20 mg/kg)组和毛蕊花糖苷低、中、高剂量(30 mg/kg、60 mg/kg、120 mg/kg)组,每组18只。采用慢性不可预见性温和应激(chronic unpredictable mild stress,CUMS)结合孤养的方式制备大鼠抑郁模型。氟西汀组和毛蕊花糖苷各剂量组分别按剂量连续灌胃给药3周,对照组和模型组每日以等体积生理盐水灌胃。采用旷场实验和糖水偏好实验观察大鼠抑郁样行为变化;免疫荧光组化法检测大鼠前额叶皮层ERS通路的关键因子葡萄糖调节蛋白78(glucose-regulated protein 78,GRP78)和C/EBP同源蛋白(C/EBP homologous protein,CHOP)的表达情况;分光光度计检测大鼠前额叶皮层caspase-3的活性。结果:与对照组比较,模型组、氟西汀组及毛蕊花糖苷各剂量组大鼠旷场实验总行程、中间停留时间及糖水摄取量均下降,前额叶皮层GRP78和CHOP的表达均明显增加,caspase-3酶活性明显升高(P0.05);与模型组比较,氟西汀组和毛蕊花糖苷各剂量组旷场实验总行程、中间停留时间及糖水摄取量均增加,GRP78和CHOP的表达均明显降低,caspase-3酶活性明显下降(P0.05)。结论:毛蕊花糖苷可以改善抑郁症大鼠的抑郁样行为,其机制可能与其抑制前额叶皮层ERS通路并减少神经元凋亡有关。     

硫酸茯苓多糖对抑郁症大鼠海马AMPA受体表达的影响

目的:探讨硫酸茯苓多糖(SP)是否通过调节AMPA受体GluR1的表达而生产抗抑郁作用。方法:实验设假手术组、抑郁症模型组、SP(25、50、100 mg/kg)三个给药组及SP(100 mg/kg)+AMPA受体抑制剂GYKI 52466组,每组动物12只。抑郁症动物模型采用卵巢摘除加慢性不可预知性温和应激(CUMS)法制备。连续灌胃和(或)腹腔注射给药21天。糖水消耗、强迫游泳及敞箱试验观察动物行为变化。海马神经元病理变化采用尼氏染色法检测。GluR1、p-GluR1、CREB、p-CREB和BDNF的蛋白表达采用免疫组化和(或)Western Blot法检测。结果:与模型组相比,SP各组大鼠强迫游泳不动时间(FSIT)明显降低而自发活动(SA)明显增加、糖水摄入量(SC)及糖水偏爱百分比(PSC)明显升高(P0.05或P0.01)、海马神经元损伤显著减轻、GluR1和GluR1磷酸化水平及p-CREB、BDNF的表达均明显升高。但与SP(100 mg/kg)剂量组相比,SP+GYKI 52466剂量组大鼠FSIT又明显增加而SA又明显减少,SC及PSC又明显降低,海马GluR1、p-GluR1及p-CREB、BDNF的表达又明显降低(P0.01)。结论:SP可能通过上调海马GluR1受体的表达,增强GluR1受体功能,促使CREB磷酸化水平升高而上调BDNF的蛋白表达而产生抗抑郁作用。     

创伤后应激障碍大鼠前额叶皮质PKMζ表达的变化

目的探讨创伤后应激障碍(PTSD)大鼠前额叶皮质PKMζ的表达变化情况。方法采用单程长时应激(SPS)制备PTSD大鼠模型,旷场试验、高架十字迷宫试验检测造模效果。将大鼠分为:SPS1d、SPS3d、SPS7d和SPS14d组,正常饲养大鼠作为对照组。利用Western blot和real-time RT-PCR检测PKMζ蛋白及m RNA在大鼠前额叶皮质表达。结果 SPS模型大鼠表现出明显的焦虑症状,SPS7d、SPS14d组大鼠前额叶皮质PKMζ蛋白和m RNA表达水平显著高于对照组。结论在应激后7d和第14d,PTSD大鼠前额叶皮质PKMζ表达显著增高。     

Secular change in menarche in women in Madrid

The age at menarche was estimated by recollection in 1617 women between the ages of 18 and 60 in Madrid and a nearby suburb, Pinto. The population of Pinto is working-class and the Madrid group, taken from residential neighbourhoods , belongs to the upper middle class. In both groups we found a diminution in average age at menarche, from 14.04 to 13.02 years in Madrid and from 14.55 to 13.16 years from about 1935 to about 1965 in Pinto. These changes have been more intense in the group which is less well-off economically, where living conditions have varied much more drastically.     

Intestinal helminthiasis in school children in Haiti in 2002

A survey on intestinal helminths in school children was conducted in Haiti in 2002. This first nationwide study involving the entire country was stratified by department according to urban and rural zones using the cluster method. Focusing on elementary school children (n=5792; age range 3 to 20 years), it involved 26 urban and 49 rural schools randomly selected. Stools were preserved in formalin and examined by the Ritchie technique. Thirty-four per cent of stools (1981/5792) tested positive for intestinal helminths with the following parasites identified: Ascaris lumbricoides (27.3%), Trichuris trichiura (7.3%), Necator americanus (3.8%), Hymenolepsis nana (2%), Taenia sp. (0.3%) and Strongyloides stercoralis (0.2%). The helminth prevalence was higher in rural (38.4%) compared to urban areas (30%). There was no significant difference in prevalence by sex and age. The importance of geohelminths changed from one department to another with the highest prevalence found in the Southern department of Grande Anse (73.7%) and the lowest prevalence in the Center department (20.6%). Five out of the country's nine departments had a similar prevalence varying from 25.5% to 28.2%. Intestinal helminthic polyparasitism was observed in a percentage of infested school children comprise between 3.4% and 28.6% according in relation to the geographical area. A program to fight against geohelminths in school children should be initiated as a public health priority. Albendazole is the drug of choice. Frequency of drug distribution should be based on the prevalence of geohelminths in each department.     

Experience in adult population in dengue outbreak in Delhi

A dengue outbreak has recently hit the Indian capital. We studied the clinical profile of adult patients. Five hundred and sixty patients of dengue infection were admitted in a specially created ward according to the criteria laid down by WHO. Haematemesis (28.28%), epistaxis (26.78%) and malena (14.28%) were some of the common presentations. Similarly lymphadenopathy, especially cervical (30.89%), palatal rashes (26.96%) and hepatomegaly (23.75%) were the most commonly encountered findings on physical examination. Most of the cases were of dengue fever with haemorrhage and only 2.5% cases were classified under dengue haemorrhagic fever or dengue shock syndrome. The average hospital stay was 3.4 days but only 9.8 hours in the eleven patients who died, suggesting their late arrival in preterminal situation giving little time for resuscitation. Thrombocytopenia was not a feature and only 12.85% patients had platelet count less than 70,000/cmm. Most of the patients who were admitted with thrombocytopenia, showed normalization in their platelet counts in next few days. Serological examination demonstrated evidence of recent dengue infection in 41.17% patients. Few patients required blood or platelet concentrate transfusion. Eleven patients died, three due to DIC, one of intracranial haemorrhage and seven due to massive gastric haemorrhage. Rest of the patients recovered completely. Thus we can conclude that recent outbreak in Delhi was of dengue fever with haemorrhage and mortality was very low in patients who came early to the hospital.     

Changes in the hypothalamic nuclei in in experimental allergy

Summary In rabbits subjected to prolonged sensitization and in which the Arthus phenomenon was induced there was a marked reaction of the hypothalamic nuclei. Staining by Gomori's method indicated a cellular swelling, loss of granules, and protoplasmic vacuolization in the supraoptic nucleus. There was a considerable increase in the size of the cross-sectional area of the cells. The same effects were much less well shown in the paraventricular nucleus. These results show that marked signs of increased neurosecretion developed in the animals at the height of the Arthus phenomenon.(Presented by Active Member AMN SSSR V. V. Parin) Translated from Byulleten Éksperimental'noi biologii i Meditsiny, Vol. 55, No. 4, pp. 110–113, April, 1963.     

Development in in vitro toxicology

There are three principal pressures driving the development of in vitro toxicology: (1) the need for more efficient testing systems to cope with the large number of xenobiotics currently being developed; (2) public pressure to reduce animal experimentation; and (3) a need for a better understanding of the mechanisms of toxicity. Within this, in vitro toxicology is focused on local, systemic, and target-organ toxicity. It is becoming increasingly apparent that a step or decision-tree approach using input of a variety of experimental data (physicochemical properties, biokinetics, cytotoxicity) provides the most efficient system for predicting toxicity. Examples of the use of in vitro toxicity systems for prediction of systemic toxicity and target-organ (liver) toxicity are presented.Originally presented at ECCP 93.