DR_4的激活在治疗阿尔茨海默病应用中的新研究  

New study about DR_4's activation on application in the treatment of Alzheimer's disease

作　　者：毛细江 黄丹 王宏伟[1] 王昌权[1] 路承彪[1] 涂强[3] 

机构地区：[1]长江大学医学院,荆州434023 [2]湖北省大冶市人民医院,黄石435100 [3]长江大学附属第一临床医院神经内科ICU,荆州434023

出　　处：《江西医药》2017年第3期200-203,共4页Jiangxi Medical Journal

基　　金：湖北省医学领军人才计划

摘　　要：目的探讨DR_4的激活对海马神经元树突棘形态学的影响,进而探讨阿尔茨海默病的发病机制及治疗新方法。方法30只Wistar雄性大鼠随机分正常组、模型组和治疗组,每组10只。正常组不做特殊处理,模型组经脑海马内注射10μl的Aβ1-42^([2])建造模型,治疗组于造模成功后第2d开始每天向脑海马内注入100μM的PD168077,连续注射1个月。通过Morris水迷宫实验对各组鼠行为学进行观察,评估并分析造模效果和药物疗效。在完成评估分析后对各组鼠脑海马组织切片行高尔基染色,用带摄像功能的Lecia显微镜观察脑片并拍照,然后用Image J图像处理软件分析海马神经元树突棘形态结构变化。结果大鼠经注射10μl的Aβ1-42后成功建立起AD模型。Morris水迷宫实验结果显示:隐藏平台实验中,模型组潜伏期和游泳距离均明显长于正常组和治疗组(N=10,P<0.01);在反向隐藏平台测试实验中,正常组和治疗组潜伏期时间及游泳距离均较模型组短(N=10,P<0.05);游泳速度各组之间无统计学差异(P>0.05)。各组海马神经元高尔基染色结果显示:正常组神经元树突棘数为34.60±5.37/10μm,模型组神经元树突棘数为25.40±7.93/10μm,治疗组神经元树突棘数为29.60±5.95/10μm(N=10,P<0.05)。结论 DR_4的激活可以改善由Aβ1-42引起的认知功能障碍,并对海马神经元树突棘及突触可塑性存在改善作用。Objective The purpose of activating dopamine D4 receptors by its agonist PD168077[1] is in order to study the morphological effect on dendritic spines in rats hippocampal neurons after DR4 being activated,and discuss the pathogenesis of AD and its new treatment methods. Methods 30 male Wistar rats were randomly assigned to the normal group,model group and treatment group,10 rats per group. No special processing on normal group,we continuously inject 100μM of PD168077 into the treatment group rats＇ hippocampus the next day after injecting 10μl of Aβ1-42[2] into the model group rats＇ hippocampus for thirty days.The following step is to observe the behavioral changes of rats for every group by Morris water maze experiment,then note,evaluate and analyse the constructing process of AD model rats and the effect of PD168077 on treating them. The last step is to make brain slices of three groups rats＇ hippocampus and stain them with Golgi Kit,take pictures with Lecia microscope,observe and analyse the changes of the dendritic spines with Image J software. Results First of all we build the AD model successfully by Aβ1-42. The results of Morris water maze experiment：the latent period and swimming distance of model group rats are significantly longer than the normal group and treatment group either in hidden platform experiments or in hidden the reverse platform experiments（N=10,P〈0.05）;Swimming speed has no statistical difference between three groups（P〉0.05）. The results of Golgi stainning for brain slices of three groups rats：the number of dendritic spines of the normal groupis 34.60±5.37/10μm,the number of model groupis 25.40±7.93/10μm,the number oftreatmentgroup is 29.60±5.95/10μm（N=10,P〈0.05）. Conclusion The activation of DR4 not only can improve the decrease of cognitive dysfunction caused by Aβ1-42,but also raise the plasticity of dendritic spines and synapsis in hippocampal neurons.

关 键 词：PD168077 树突棘 海马 阿尔茨海默病 DR4激动剂 高尔基染色 

分 类 号：R749.16[医药卫生—神经病学与精神病学]