MPTP慢性帕金森病小鼠海马内氧化应激与细胞凋亡蛋白的表达

目的 观察 MPTP慢性帕金森病小鼠海马氧化应激指标及细胞凋亡相关蛋白的表达.方法 应用MPTP制备慢性帕金森病模型,观察行为学改变,Morris水迷宫实验,检测模型组和对照组小鼠海马内超氧化物歧化酶（SOD）、还原型谷胱甘肽（GSH）及丙二醛（MDA）舍量变化,以及免疫组织化学方法、RT-PCR方法、Western blot方法检测海马Bax和Bel-2蛋白表达.结果 慢性帕金森病模型小鼠行为学特点为震颤、活动减少;水迷宫实验结果提示认知功能降低;与对照组海马比较：模型组海马SOD、GSH含量均下降,而MDA含量升高（P〈0.05）;模型组海马Bax蛋白表达增高,而Bel-2蛋白表达下降（P〈0.05）.结论 氧化应激在慢性帕全森病认知功能障碍发病机制中起重要作用,而Bax和Bcl-2蛋白参与了氧化应激诱导海马神经元凋亡的调控过程.     

MPTP致C57BL/6小鼠帕金森病模型的复制及常用的行为学分析方法

目的介绍1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱发C57BL/6小鼠的帕金森病(Parkinson disease,PD)模型的复制及常用的行为学分析方法。方法C57BL/6小鼠腹腔注射MPTP(40 mg/kg),每天1次,连续注射7 d;同时每天进行小鼠的爬杆实验、悬挂实验、游泳实验和震颤麻痹评分;最后取材,用HPLC-ECD法测定纹状体内的多巴胺含量,用Lowry法测定纹状体内的蛋白总量,并计算多巴胺(ng)/蛋白总量(mg)的比值。结果爬杆实验结果表明,PD模型组小鼠爬杆所用的时间明显长于对照组,其分值低,对照组和PD模型组间有极显著性差异(P<0.01);悬挂实验表明PD模型组小鼠悬挂能力明显低于对照组(P<0.01);游泳实验表明PD模型组小鼠游泳能力明显低于对照组,小鼠肢体运动协调情况不好,组间有极显著性差异(P<0.01);震颤麻痹评分显示,PD模型组分值很高,震颤麻痹症状非常明显,较对照组有极显著性差异(P<0.01);多巴胺含量分析显示,PD模型组多巴胺(ng)/蛋白总量(mg)的比值明显低于对照组,有极显著性差异(P<0.01)。结论用MPTP诱发C57BL/6小鼠的帕金森病模型的复制方法以及爬杆试验、悬挂实验、游泳实验和震颤麻痹评分简单可靠,是用于帕金森病治疗研究的良好方法。     

烟碱对MPTP引起的C57BL/6小鼠黑质纹状体多巴胺能神经元损伤的保护作用

目的:1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)可引起实验动物产生类似帕金森氏病的症状和病理改变。本实验拟观察烟碱(Nicotine,Nic)对MPTP引起的小鼠黑质纹状体多巴胺能神经元损伤的预防和治疗作用。方法:C57BL/6小鼠分为2批。第1批注射MPTP后给予烟碱治疗(Nic0.1,0.5,1.0mg.kg-1,tid),第2批于注射MPTP前1d开始给予烟碱(bid)。连续用药15d后用荧光分光光度法测定纹状体的多巴胺(DA)含量。结果:与MPTP对照组比较,不同剂量Nic治疗组小鼠纹状体DA含量明显提高(P<0.05);于注射MPTP前1d开始给予烟碱的小鼠,其纹状体DA含量则显著提高,接近正常对照组的水平(90.69%～91.44%)。结论:实验结果提示烟碱对MPTP所致的神经损伤具有预防和治疗效果。     

Postconditioning of sevoflurane and propofol is associated with mitochondrial permeability transition pore

Background： Sevoflurane and propofol are effective cardioprotective anaesthetic agents, though the cardioprotection of propofol has not been shown in humans. Their roles and underlying mechanisms in anesthetic postconditioning are unclear. Mitochondrial permeability transition pore （MPTP） opening is a major cause of ischemia-reperfusion injury. Here we investigated sevoflurane- and propofol-induced postconditioning and their relationship with MPTP. Methods： Isolated perfused rat hearts were exposed to 40 min of ischemia followed by 1 h of reperfusion. During the first 15 min of reperfusion, hearts were treated with either control buffer （CTRL group） or buffer containing 20 μmol/L atractyloside （ATR group）, 3% （v/v） sevoflurane （SPC group）, 50 μmol/L propofol （PPC group）, or the combination of atractyloside with respective anesthetics （SPC＋ATR and PPC＋ATR groups）. Infarct size was determined by dividing the total necrotic area of the left ventricle by the total left ventricular slice area （percent necrotic area）. Results： Hearts treated with sevoflurane or propofol showed significantly better recovery of coronary flow, end-diastolic pressures, left ventricular developed pressure and derivatives compared with controls. Sevoflurane resulted in more protective alteration of hemodynamics at most time point of reperfusion than propofol. These improvements were paralleled with the reduction of lactate dehydrogenase release and the decrease of infarct size （SPC vs CTRL： （17.48±2.70）% vs （48.47±6.03）%, P〈0.05; PPC vs CTRL： （35.60±2.10）% vs （48.47±6.03）%,P〈0.05）. SPC group had less infarct size than PPC group （SPC vs PPC： （ 17.48±2.70）% vs （35.60±2.10）%,P〈0.05）. Atractyloside coadministration attenuated or completely blocked the cardioprotective effect of postconditioning of sevoflurane and propofol. Conclusion： Postconditioning of sevoflurane and propofol has cardio-protective effect against ischemia-reperfusion injury of heart     

Monoamine oxidase activity in single nerve cell bodies from substantia nigra of rat and man

Summary In single nerve cell bodies isolated from the substantia nigra of man and rat the active forms of MAO A and MAO B were found by the use of the microdiver technique and specific inhibitors.     

首乌制剂对MPTP引起的小鼠帕金森病的防治

实验选用成年ICR纯系小鼠，通过对小鼠主动运动以及脑内多巴胺（DA）含量的测定，观察首乌的醇提取物对MPTP引起的小鼠帕金森病的预防与治疗作用。实验发现，注射MPTP后，小鼠主动性活动明显减少，脑内DA含量明显降低，表现出帕金森病的特征。对这些小鼠再注射首乌制剂能促进小鼠的运动，脑内DA的含量得以恢复。若同时注射MPTP和首乌制剂，则小鼠主动性活动时间以及纹状体多巴胺的含量都明显高于单独注射MPTP组。实验提示，MPTP可引起ICR小鼠脑内多巴胺神经元损伤并产生帕金森病症状，而首乌制剂对MPTP的毒性作用有明显的预防作用和一定的治疗作用，这可能与首乌制剂抑制型单腔氧化酶的活性有关。     

Platelets as a model for neurones?

The multiple biochemical and pharmacological similarities existing between blood platelets and 5-hydroxytryptamine (5-HT)-containing neurones of the CNS point to the platelets as a reliable model for the biochemical characterization of 5-HT releasers and uptake blockers which interfere with the storage and the active carrier mechanism of 5-HT in the neurones, respectively. In addition, the affinity displayed by dopamine and by dopaminergic neurotoxin MPP⁺ for the platelet 5-HT transport and storage indicates also some similarities between platelets and the dopaminergic system of the CNS. Since human platelets contain almost exclusively monoamine oxidase type B (MAO-B), they can be used as a source for the purification and characterization of this human enzyme. Human platelets thus offer an excellent peripheral model to indirectly assess the degree and duration of MAO-B inhibition occurring in the CNS. To date, knowledge of the many biochemical mechanisms underlying platelet physiology is still fragmentary. In fact, the functional role of binding sites located on the platelet cytoplasmic membrane, i.e. their coupling to a specific transmembrane signalling mechanism, is still in need of a precise biochemical and physiological characterization.     

制备偏侧帕金森病猴模型的术前准备及术后护理

摘要: 目的 概述偏侧帕金森病猴模型术前准备中需要注意的事项及术后护理心得。方法 选取猕猴 10 只,经股 动脉介入方法对一侧颈内动脉注射 1-甲基-4-苯基-1 ,2 ,3 ,6-四氢吡啶( MPTP) ,建立偏侧性帕金森病( PD) 猴模 型,在术前、术后积极实施相关护理措施。重点涉及到驯养技巧、手术前后的常规护理、并发症防治及饲养管理等 方面的内容。结果 所有猕猴均成功注药,术后生存率为 80% 。结论 成熟的手术方法对模型制作固然重要,精心的护理和完善的准备却是保障动物生命安全以及术后迅速恢复的关键环节。     

更年期女性帕金森病动物模型的建立与评价

通过建立去卵巢帕金森病小鼠模型，应用免疫组织化学染色、逆转录一聚合酶链式反应及高效液相色谱法等多项技术对小鼠黑质多巴胺神经元数目、基因表达水平及纹状体多巴胺及其代谢物含量进行考察并评价。实验结果表明模型组小鼠上述检测指标较对照组均明显减少（P〈O．01）。发现本模型具有更年期女性帕金森病的基本的病理特点，可应用于临床研究。