呱醋甲酯、瑞波西汀对注意缺陷多动障碍大鼠注意定势转移能力的影响

目的通过测评注意缺陷多动障碍(ADHD)动物模型幼年自发性高血压大鼠(SHR)的注意定势转移能力,探讨呱醋甲酯(利地林)和瑞波西汀对ADHD大鼠模型注意定势转移能力的改善作用。方法4周雄性SHR27只随机分为SHR呱醋甲酯组(SR)9只、SHR瑞波西汀组(SRB)10只和SHR生理盐水对照组(SN)8只,WKY大鼠对照组(WN)8只。SR组腹腔注射"呱醋甲酯"5mg.kg-1.d-19d,SRB组腹腔注射瑞波西汀10mg.kg-1.d-19d,SN对照组按同期对照原则注射等量生理盐水。投药的第6～9d连续完成注意定势转移能力测评,记录评定注意定势转移任务的循环数。结果①SHR在简单辨别阶段(SD)、复杂辨别阶段(CD)、复杂辨别反向阶段(CDR)、内维度转换阶段(IDS)、外维度转换阶段(EDS)能够连续6次正确完成操作任务所需要的次数明显多于WKY大鼠(P<0.05～P<0.01)。②SR组大鼠在上述所有阶段完成任务所需要的循环次数都较SN对照组减少(P<0.05),不过在内维度转换反向阶段(IDSR)两组差异无统计学意义(P>0.05)。③SRB组大鼠在完成所有阶段任务所需要的循环次数都较SN对照组减少(P<0.05),不过在复习辨别反向阶段(CDRre)两组差异无统计学意义(P>0.05)。结论幼年SHR存在注意定势转移能力缺陷,"呱醋甲酯"和瑞波西汀均可以改善SHR注意定势转移能力。     

阿托伐他汀对自发性高血压大鼠动脉血压和血管内皮功能的影响

目的探讨阿托伐他汀对自发性高血压大鼠(SHR)动脉血压和血管内皮功能的影响。方法选用8周龄SHR12只,随机分为阿托伐他汀治疗组(ATV组,n=6)、蒸馏水组(DW组,n=6),另选6只WKY大鼠作为正常对照。ATV组大鼠给以阿托伐他汀50mg/(kg·d)加适量蒸馏水灌胃。DW组和WKY组每天同时用等量蒸馏水灌胃。观察给药前后大鼠尾动脉血压的变化,测定大鼠血清总胆固醇(TC)、甘油三酯(TG)和高密度脂蛋白胆固醇(HDL-C)浓度,观察血浆内皮素1(ET-1)水平、主动脉组织一氧化氮合酶(NOS)活性的变化特点。结果ATV组大鼠动脉血压显著低于DW组(P＜0．01)；与DW组和WKY组比较,ATV组血清TC、TG和HDL-C浓度显著降低(P＜0．01,P＜0．05)；DW组血清ET-1水平显著高于WKY组(P＜0．05),主动脉组织NOS活性显著低于WKY组(P＜0．05),经ATV治疗后血清ET-1水平明显降低(P＜0．05),而主动脉组织NOS活性显著增高(P＜0．01)。结论长期应用阿托伐他汀可以显著降低动脉血压。阿托伐他汀通过改善血管内皮功能延缓高血压的病理过程。     

SHR大鼠脑出血急性期血压调控机制与NE、E、PRA、Ang Ⅱ关系

目的 研究自发性高血压大鼠脑出血急性期血压调控机制与去甲肾上腺素(NE)、肾上腺素(E)、血管紧张素Ⅱ(AngⅡ)、肾素(PRA) 关系,探讨脑出血急性期血压调控机制. 方法 采用胶原酶注入尾状核的方法建立大鼠脑出血模型,利用高效液相-电化学法、放射免疫方法测定出血前及出血后1 d、3 d、7 d和14 d 5个时间点(即 5个组)血浆NE、E、AngⅡ、PRA及下丘脑NE、AngⅡ的含量. 结果 (1)血浆NE、E及下丘脑NE含量在脑出血1 d时达高峰[分别为(4.31±0.97)μg/L、(8.55±2.41)μg/L、(919±128)ng/g],与术前比较差异有统计学意义(P<0.05),7～14 d基本恢复至术前水平;(2)血浆PRA、AngⅡ及下丘脑AngⅡ含量在出血后3 d达到高峰[分别为(8.81±3.1)ng/mL·h、(1204±269)pg/mL、(33.6±7.1)pg/mg],与术前比较差异有统计学意义(P<0.05),7～14 d基本恢复至术前水平;(3)大鼠脑出血第1天血压较术前明显升高,差异有统计学意义(P<0.05),第3天较第]天明显下降,7～14d基本恢复至出血前水平. 结论 SHR大鼠脑出血急性期血压调控可能与交感-肾上腺髓质系统及肾素-血管紧张素系统在脑出血急性期的应激性激活密切相关.     

氯沙坦对自发性高血压大鼠肾素—血管紧张素II水平的影响

目的：运动物验观察氯沙坦对自发性高血压大鼠（ＳＨＲ）血浆、下丘脑肾活性（ＲＡ）和血管紧张素ＩＩ（ＡｎｇＩＩ）水平的影响。方法：１６只雄性６周龄ＳＨＲ随机分为氯沙坦治疗组（ＳＨＲ＋Ｌ）和对照组（ＳＨＲ），另以８只同龄雄性Ｗｉｓｔａｒ－Ｋｙｏｔｏ大和为正常对照组（ＷＫＹ），氯沙坦组按３０ｍｇ．ｋｇ＾－１，氯沙坦组按３０ｍｇ．ｋｇ＾－１．ｄ＾－１约药，用药１８周后采用放免法检测血浆和下丘脑中ＲＡ和Ａｎｇ     

自发性高血压大鼠的脑白质损伤及其炎症反应机制

目的 通过观察自发性高血压大鼠(SHR)脑白质损伤的病理改变和检测炎症相关指标,探讨炎症反应在SHR脑白质损伤中的作用. 方法 选择18只40周龄雄性SHR为实验组,同龄7只雄性Wistar-Kyoto(WKY)大鼠为对照组,取动物脑组织,应用HE染色及免疫组织化学染色,观察其病理改变及胶质酸性蛋白、神经中丝、髓鞘碱性蛋白的含量改变.同时取大鼠脑白质组织,使用荧光实时定量PCR技术,检测Toll样受体4(TLR-4)和单核细胞趋化蛋白1(MCP-1)以及与血管细胞黏附分子1(VCAM-1)的mRNA表达水平. 结果 40周龄SHR脑白质出现明显损伤.HE染色显示出现脑白质疏松,免疫染色显示白质区星形胶质细胞活化、神经轴索数量减少以及脱髓鞘改变.相对于WKY,SHR脑白质TLR-4、MCP-1和VCAM-1的mRNA表达明显增高,差异有统计学意义(P＜0.05);相对于脑白质损伤程度较轻的SHR,程度较重的SHR中TLR-4、MCP-1和VCAM-1 mRNA表达水平更高,差异有统计学意义(P＜0.05). 结论 SHR脑白质损伤情况与脑白质疏松症类似;炎症反应参与脑白质损伤的病理生理过程,是导致脑白质损伤的因素之一.     

吡格列酮对糖尿病大鼠中枢神经系统PPAR-γ表达的影响

目的 研究吡格列酮对糖尿病大鼠海马、下丘脑处PPAR-γ表达的影响及与大鼠认知功能的关系.方法 雄性SD大鼠随机分为对照组(C组)、糖尿病组(D组)、糖尿病+吡格列酮组(DP组),每组10只.8周后行Morris水迷宫评价大鼠的空间学习记忆能力,Western Blot方法检测大鼠海马、下丘脑处PPAR-γ表达水平.结果 Morris水迷宫中,D组大鼠逃避潜伏期较C组和DP组延长差异均有统计学意义(P<0.05).大鼠海马和下丘脑处,PPAR-γ的表达D组较C组减少,DP组较D组增多,差异均有统计学意义(P<0.05).结论 吡格列酮能够增加糖尿病大鼠海马、下丘脑组织局部PPAR-γ表达水平,并且这种表达的增加可能是吡格列酮改善糖尿病大鼠空间学习记忆能力的机制之一.     

吡格列酮对糖尿病大鼠中枢神经系统11β-羟类固醇脱氢酶1 型表达的影响

目的 研究吡格列酮对糖尿病大鼠海马、下丘脑处11β-羟类固醇脱氢酶1型(11β-HSD1)表达的影响及与认知功能的关系.方法 雄性SD大鼠随机分为对照组(C组)、糖尿病组(D组)、糖尿病+吡格列酮治疗组(DP组),每组10只.8周后行Morris水迷宫评价大鼠的认知功能,Western Blot方法检测大鼠海马、下丘脑处11β-HSD1表达水平.结果 Morris水迷宫中,D组大鼠穿越原平台区次数较C组减少,DP组大鼠较D组增多,差异有统计学意义(P<0.01).在海马和下丘脑处,11β-HSD1表达D组较C组增加,DP组较D组减少,较C组增加,差异有统计学意义(P<0.01).结论 吡格列酮能够降低糖尿病大鼠海马、下丘脑组织局部11β-HSD1表达水平,并且可能是吡格列酮改善糖尿病大鼠空间学习记忆能力的机制之一.     

急性应激对大鼠脑内5-羟色胺2A受体mRNA表达的影响

目的　探讨急性应激对大鼠脑内 5 羟色胺 2A (5 HT2A)受体mRNA表达的影响。方法将 1 2只雄性Sprague Dawley大鼠随机分为应激组和对照组 ,每组 6只。根据 5 HT2A受体互补DNA(cDNA)序列合成相应的特异性引物 ,用聚合酶链反应 (PCR)方法观察强迫游泳应激后 3h大鼠海马、下丘脑和中脑 5 HT2A受体mRNA的表达 ,并测定各脑区阳性电泳条带密度与 β 肌动蛋白密度的百分比。结果　 (1 )应激组和对照组大鼠海马、下丘脑和中脑均存在 5 HT2A受体 (61 1bp)mRNA的表达 ;5 HT2A受体PCR产物序列与已知的 5 HT2A受体cDNA序列一致 ;(2 )应激组大鼠海马、下丘脑和中脑5 HT2A受体mRNA表达的相对水平分别为 (53± 5) %、(63± 8) %和 (47± 7) % ,均分别明显高于对照组[(42± 4) % ,(33± 6) %和 (2 7± 7) % ] ,t值分别为 4 .545 ,7.0 83 ,4.92 3 ,P均 <0 0 1。结论　急性应激后大鼠海马、下丘脑和中脑 5 HT2A受体mRNA的表达增多     

急性应激对大鼠脑内5-羟色胺1A受体mRNA表达的影响

目的 探讨急性应激对大鼠脑内5-羟色胺1A(5-HT1A)受体mRNA表达的影响。方法 将12只雄性Sprague-Dawley大鼠随机分为应激组和对照组,每组6只。根据5-HT1A受体互补DNA(eDNA)序列合成相应的特异性引物,用聚合酶链反应(PCR)法观察强迫游泳应激后3 h大鼠海马、下丘脑和中脑5-HT1A受体mRNA表达,并测定各脑区阳性电泳条带密度与β肌动蛋白(β-actin)密度的百分比。结果 应激后3 h,大鼠下丘脑5-HT1A受体mRNA表达相对水平为(64.3±6.7)％,显著低于对照组(78.9±8.7)％(t=3.263.P<0.05);海马、中脑5-HT1A受体mRNA表达相对水平分别为41.5％±7.1％、37.4％±5.6％,均分别显著低于对照组64.8％±9.6％、63.9％±6.3％(t分别为4.782、7.701,P均<0.01)。结论 急性应激后大鼠海马、下丘脑和中脑5-HT1A受体mRNA的表达降低。     

大鼠抑郁性神经症模型下丘脑单胺类神经递质研究

我们在建立大鼠抑郁性神经症模型的基础上 ,应用高效液相色谱 ＥＣ法观察其下丘脑内单胺类神经递质的变化 ,旨在进一步探讨抑郁性神经症的发病机理。材料和方法　 ( 1 )动物模型 :动物为成年ＳＤ雄性大鼠 ,体重 1 80～ 2 2 0ｇ(南京中医药大学动物实验中心提供 )。首先用Ｏｐｅｎ Ｆｉｅｌｄ法作行为学评分[1 ] ,选择得分相近的 2 0只大鼠随机分为对照组和模型组 ,每组 1 0只。模型组每笼饲养 1只 ,对照组每笼饲养 5只。模型组共接受 2 1天各种不同的应激 ,包括冰水游泳 ( 4℃ ,5ｍｉｎ)、热应激 ( 45℃ ,5ｍｉｎ)、禁水 ( 2 4ｈ)、夹尾 ( …     

Denervation study of synapses of organ of corti of old world monkeys

Fine structural characteristics of synapses in the spiral organ of Corti were examined, with reference to differences between inner and outer haircell systems, and to location of neurons of origin of efferent axons. Surgical interruption of crossed olivocochlear bundle, of vestibular nerve, of facial nerve, and excision of superior cervical ganglia were used to determine the pathways of efferent axons. Interruption of the vestibular nerve near the brainstem results in degeneration of all efferent terminals on outer hair cells. Mid-line lesions at, and caudal to, the facial colliculus result in degeneration of about half of these efferent terminals. Efferent synaptic bulbs to the inner hair-cell system are small, of the order of one micron, and form type 2 junctions with afferent dendrites. They tend to have more large dense-core vesicles (about 80 nm) than the large efferent terminals of the outer hair-cell system, and appear to be the terminals of axons in the habenula perforata, which exhibit varicosities laden with large dense core vesicles. The varicosities are unaffected by excision of the superior cervical ganglia. So far as our material can reveal, it appears that the varicosities in the habenula perforata do not survive vestibular root interruption, nor do the efferent processes in the internal spiral bundle or at the base of inner hair cells. Most interestingly, the afferent processes of the inner hair-cell system, as identified for example by their relation to pre-synaptic bodies in the inner hair cells, are subject to a trans-synaptic reaction after severance of the vestibular root. They undergo a dramatic cytological transformation, characterized by increase of volume, engorgement with microtubules, microfilaments, microvesicles of various sizes, and clusters of lysosomes. Thus, both the efferent and afferent terminals of the inner hair-cell system show marked cytological differences from the corresponding terminals of the outer hair cell system.     

Mechanism of action of tubocurarine on nicotinic cholinoreceptors of neurons of the sympathetic ganglia of rats

Tubocurarine (Tc) effect on membrane currents elicited by acetylcholine (ACh) was studied in isolated superior cervical ganglion neurons of rat using patch-clamp method in the whole-cell recording mode. The "use-dependent" block of ACh current by Tc was revealed in the experiments with ACh applications, indicating that Tc blocked the channels opened by ACh. Mean lifetime of Tc-open channel complex, tau, was found to be 9.8 +/- 0.5 s (n = 7) at -50 mV and 20-24 degrees C. tau exponentially increased with membrane hyperpolarization (e-fold change in tau corresponded to the membrane potential shift by 61 mV). Inhibition of the ACh-induced current by Tc (3-30 microM/1) was completely abolished by membrane depolarization to the level of 80-100 mV. Inhibition of ACh-induced current was augmented at increased ACh doses. It is concluded that the open channel block produced by Tc is likely to be the only mechanism for Tc action on nicotinic acetylcholine receptors in superior cervical ganglion neurons of rat.     

The effect of age of onset of PD on risk of dementia

Background Dementia occurs in the majority of patients with Parkinson’s disease (PD). Late onset of PD has been reported to be associated with a higher risk for dementia. However, age at onset (AAO) and age at baseline assessment are often correlated. The aim of this study was to explore whether AAO of PD symptoms is a risk factor for dementia independent of the general effect of age. Methods Two community-based studies of PD in New York (n = 281) and Rogaland county, Norway (n = 227) and two population-based groups of healthy elderly from New York (n = 180) and Odense, Denmark (n = 2414) were followed prospectively for 3–4 years and assessed for dementia according to DSM-IIIR. All PD and control cases underwent neurological examination and were followed with neurological and neuropsychological assessments. We used Cox proportional hazards regression based on three different time scales to explore the effect of AAO of PD on risk of dementia, adjusting for age at baseline and other demographic and clinical variables. Findings In both PD groups and in the pooled analyses, there was a significant effect of age at baseline assessment on the time to develop dementia, but there was no effect of AAO independent of age itself. Consistent with these results, there was no increased relative effect of age on the time to develop dementia in PD cases compared with controls. Interpretation This study shows that it is the general effect of age, rather than AAO that is associated with incident dementia in subjects with PD. Received in revised form: 22 December 2005     

Limits of deinstitutionalization--perspectives of relatives of psychiatric patients

After a hopeful beginning, the social process of the reintegration of those with severe mental illness has come to a standstill. I am led to wonder whether "the community" really wants to live together with people suffering from severe mental illness, and if so, how closely? As long as the medical treatment of mental illness provided by the general practitioners is fundamentally deficient, as they are not able to prescribe the necessary interventions--such as out-patient psychiatric nursing, and service providers in the out-patient sector are content with offering increasingly intensive forms of care for the less seriously ill at the cost of the Social Welfare System--the reintegration of those with serious mental illness remains an illusion--which is mainly to the benefit of providers of residential care in homes and hostels.