孤独症谱系障碍仔鼠模型脑组织CaMKⅡ和ERK表达的相关研究

发布时间：2018-10-30 10:04

【摘要】：目的:观察孤独症谱系障碍仔鼠模型Ca2+-CaM-CaMKII-ERK信号转导通路的改变情况,探讨其仔鼠模型脑组织中CaMKII和ERK的表达是否存在异常及其是否在孤独症谱系障碍发病机制中发挥作用。方法:实验组采用孕十二天半的大鼠腹腔注射丙戊酸钠(按250 g/L溶于生理盐水中),其仔鼠为实验组;对照组孕鼠注射同量生理盐水,其仔鼠为对照组。对两组仔鼠均进行生长发育及相关行为学检测。生长发育检测:仔鼠体重,睁眼情况及游泳协调性等检测;交往及非交往行为检测:跟随、攀爬,嗅探同伴,为同伴整理毛发,自我修饰及区域探索等;交流检测:社交及非社交性行为检测;刻板重复动作检测:仔鼠理毛、蹦跳、转圈等行为。使用形态学和图像分析技术检测,观察并比较五个不同日龄(1、7、14、21、28天)两组仔鼠额皮质中CaMKII、ERK的表达情况。结果:仔鼠模型鉴定:与对照组相比,实验组仔鼠在发育学方面表现为发育迟缓、体重低、睁眼延迟、游泳协调性差、方向趋向反应异常、社交行为减弱、时间短暂、刻板重复行为增多、社会取向和社会交流异常等。HE染色:1天、7天的实验组仔鼠大脑皮质神经元数量较稀疏,14天神经元数量明显增加,之后一直高于对照组仔鼠的神经元数量;免疫组织化学染色:1~14天两组CaMKII和ERK的积分光密度值均增高(P0.001),且实验组仔鼠CaMKII和ERK的积分光密度值显著高于对照组(P0.001),14天时最为显著,P0.001,21天两组无明显差异(P0.05),28天后两组CaMKII和ERK的表达趋于稳定,差异不具有统计学意义(P0.05)。结论:孤独症谱系障碍仔鼠模型脑组织额皮质CaMKII和ERK表达异常;孤独症谱系障碍仔鼠模型脑组织额皮质CaMKII和ERK表达在时间上具有一致性;孤独症谱系障碍仔鼠模型中枢神经系统神经元存在先过度表达后出现发育迟缓甚至停滞的现象。
[Abstract]:Objective: to observe the changes of Ca2-CaM-CaMKII-ERK signal transduction pathway in rat model of autism spectrum disorder. To investigate the abnormal expression of CaMKII and ERK in the brain of the rat model and whether they play a role in the pathogenesis of autism spectrum disorder. Methods: rats in the experimental group were intraperitoneally injected with sodium valproate (250 g / L dissolved in normal saline) and the pregnant rats in the control group were injected with the same amount of normal saline. The growth and development of both groups were measured. Growth and development test: body weight, eye opening and swimming coordination, association and non-communication behavior: follow, climb, sniff companion, finishing hair for peer, self-modification and regional exploration, etc. Communication testing: social and non-social behavior testing; stereotypical repetitive action detection: cupping, bouncing, spinning, and so on. Morphological and image analysis techniques were used to observe and compare the expression of CaMKII,ERK in the frontal cortex of the two groups. Results: compared with the control group, the experimental group showed developmental retardation, low weight, delayed eye opening, poor coordination of swimming, abnormal orientation, weak social behavior and short time. HE staining showed that the number of neurons in the cerebral cortex of the experimental group on day 1 and day 7 was sparse, and the number of neurons increased significantly at day 14. The number of neurons was higher than that of the control group. Immunohistochemical staining: 1 the integral optical density of CaMKII and ERK in the two groups increased significantly (P0.001) on the 14th day, and the integral optical density of CaMKII and ERK in the experimental group was significantly higher than that in the control group (P0.001), and the most significant at the 14th day. After 28 days, the expression of CaMKII and ERK tended to be stable, the difference was not statistically significant (P0.05). Conclusion: the expression of CaMKII and ERK in frontal cortex of juvenile rats with autism spectrum disorder is abnormal, and the expression of CaMKII and ERK in frontal cortex of juvenile rats with autism spectrum disorder is consistent in time. The neurons of central nervous system (CNS) of the rat model of autism spectrum disorder were overexpressed first and then retarded or even stagnated.
【学位授予单位】：佳木斯大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R749.94;R-332

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