發(fā)布時間：2018-10-30 10:04

【摘要】：目的:觀察孤獨癥譜系障礙仔鼠模型Ca2+-CaM-CaMKII-ERK信號轉(zhuǎn)導(dǎo)通路的改變情況,探討其仔鼠模型腦組織中CaMKII和ERK的表達是否存在異常及其是否在孤獨癥譜系障礙發(fā)病機制中發(fā)揮作用。方法:實驗組采用孕十二天半的大鼠腹腔注射丙戊酸鈉(按250 g/L溶于生理鹽水中),其仔鼠為實驗組;對照組孕鼠注射同量生理鹽水,其仔鼠為對照組。對兩組仔鼠均進行生長發(fā)育及相關(guān)行為學(xué)檢測。生長發(fā)育檢測:仔鼠體重,睜眼情況及游泳協(xié)調(diào)性等檢測;交往及非交往行為檢測:跟隨、攀爬,嗅探同伴,為同伴整理毛發(fā),自我修飾及區(qū)域探索等;交流檢測:社交及非社交性行為檢測;刻板重復(fù)動作檢測:仔鼠理毛、蹦跳、轉(zhuǎn)圈等行為。使用形態(tài)學(xué)和圖像分析技術(shù)檢測,觀察并比較五個不同日齡(1、7、14、21、28天)兩組仔鼠額皮質(zhì)中CaMKII、ERK的表達情況。結(jié)果:仔鼠模型鑒定:與對照組相比,實驗組仔鼠在發(fā)育學(xué)方面表現(xiàn)為發(fā)育遲緩、體重低、睜眼延遲、游泳協(xié)調(diào)性差、方向趨向反應(yīng)異常、社交行為減弱、時間短暫、刻板重復(fù)行為增多、社會取向和社會交流異常等。HE染色:1天、7天的實驗組仔鼠大腦皮質(zhì)神經(jīng)元數(shù)量較稀疏,14天神經(jīng)元數(shù)量明顯增加,之后一直高于對照組仔鼠的神經(jīng)元數(shù)量;免疫組織化學(xué)染色:1~14天兩組CaMKII和ERK的積分光密度值均增高(P0.001),且實驗組仔鼠CaMKII和ERK的積分光密度值顯著高于對照組(P0.001),14天時最為顯著,P0.001,21天兩組無明顯差異(P0.05),28天后兩組CaMKII和ERK的表達趨于穩(wěn)定,差異不具有統(tǒng)計學(xué)意義(P0.05)。結(jié)論:孤獨癥譜系障礙仔鼠模型腦組織額皮質(zhì)CaMKII和ERK表達異常;孤獨癥譜系障礙仔鼠模型腦組織額皮質(zhì)CaMKII和ERK表達在時間上具有一致性;孤獨癥譜系障礙仔鼠模型中樞神經(jīng)系統(tǒng)神經(jīng)元存在先過度表達后出現(xiàn)發(fā)育遲緩甚至停滯的現(xiàn)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.
【學(xué)位授予單位】：佳木斯大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R749.94;R-332

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本文編號：2299691