【摘要】：研究背景及目的 隨著人類社會(huì)老齡化的進(jìn)程,癡呆的發(fā)病率也逐年增加。在癡呆人群中血管性癡呆(VD)和阿爾茲海默病(AD)占各類癡呆發(fā)病的絕大部分,其中VD發(fā)病率略高于AD。給社會(huì)和家庭帶來了嚴(yán)重的經(jīng)濟(jì)和精神負(fù)擔(dān)。近年來認(rèn)為無論是AD還是VD,均與血管因素有關(guān)。慢性腦缺血作為神經(jīng)系統(tǒng)的一種常見病理狀態(tài),是由各種原因?qū)е碌拈L期的腦灌流不足,而導(dǎo)致的腦代謝障礙和功能衰退,是血管性癡呆、Binswanger病、Alzheimer病(AD)等多種疾病發(fā)展的一個(gè)共同病理過程。腦血流低灌注在癡呆發(fā)病機(jī)制中的作用日漸成為人們關(guān)注熱點(diǎn)。為此明確癡呆的發(fā)病機(jī)制特別是在慢性腦缺血的狀態(tài)下引發(fā)的癡呆的發(fā)病機(jī)制顯得尤為重要。既往對(duì)慢性腦缺血導(dǎo)致認(rèn)知功能的研究多集中在腦代謝、腦血管損害、腦內(nèi)免疫細(xì)胞活動(dòng)、細(xì)胞凋亡、突觸結(jié)構(gòu)等方面。 Numb蛋白最初在果蠅周圍神經(jīng)系統(tǒng)的發(fā)育中被發(fā)現(xiàn)的,因其在果蠅細(xì)胞中有決定細(xì)胞命運(yùn)的作用被稱為細(xì)胞命運(yùn)決定子,隨后在哺乳動(dòng)物以及人的神經(jīng)系統(tǒng)也發(fā)現(xiàn)了同樣的功能,但哺乳動(dòng)物Numb蛋白的結(jié)構(gòu)和功能較果蠅復(fù)雜。在近年的研究中發(fā)現(xiàn)Numb作為細(xì)胞內(nèi)吞蛋白在神經(jīng)發(fā)育過程中發(fā)揮重要作用。不僅參與調(diào)節(jié)神經(jīng)前體細(xì)胞的不對(duì)稱分裂、維持神經(jīng)祖細(xì)胞的自我更新還參與調(diào)控神經(jīng)細(xì)胞遷移和神經(jīng)突生長等。本實(shí)驗(yàn)預(yù)通過檢測(cè)慢性腦缺血大鼠認(rèn)知功能的改變及海馬區(qū)Numb表達(dá)的動(dòng)態(tài)變化初步探討慢性腦缺血所致的認(rèn)知功能改變和Numb之間的關(guān)系及可能機(jī)制。為缺血性腦血管病所引起的認(rèn)知障礙的研究與治療提供理論依據(jù)。 方法 1.雄性SD大鼠40只,鼠齡大于12個(gè)月,隨機(jī)分為假手術(shù)組、缺血8周組、缺血10周組、缺血12周組4組,每組10只。 2.采用永久性雙側(cè)頸總動(dòng)脈結(jié)扎制備腦灌注不足模型(2VO模型),假手術(shù)組除不接扎雙側(cè)頸動(dòng)脈外余處理與手術(shù)組相同。 3.各組在對(duì)應(yīng)時(shí)間進(jìn)行Morris水迷宮試驗(yàn),檢測(cè)大鼠的學(xué)習(xí)和記憶功能。 4.通過免疫組化檢測(cè)大鼠海馬CA1區(qū)Numb的表達(dá)。 5.通過Western bolt檢測(cè)大鼠海馬的Numb表達(dá) 6.數(shù)據(jù)采集和數(shù)據(jù)分析。 結(jié)果 1.行為學(xué)檢測(cè)結(jié)果顯示,缺血組大鼠逃避潛伏期較假手術(shù)組明顯延長,穿越平臺(tái)次數(shù)明顯減少,且隨著缺血時(shí)間的延長,逃避潛伏期進(jìn)行性延長,穿越平臺(tái)次數(shù)進(jìn)行性減少,表明2VO術(shù)后大鼠學(xué)習(xí)記憶能力明顯受損,且隨缺血時(shí)間延長進(jìn)行性加重。 2.免疫組化半定量結(jié)果顯示,缺血組大鼠海馬CA1區(qū)Numb表達(dá)較假手術(shù)組明顯減少,并隨缺血時(shí)間的延長進(jìn)行性減少。 3.Western bolt結(jié)果顯示,缺血組大鼠海馬CA1區(qū)Numb表達(dá)較假手術(shù)組明顯減少,并隨缺血時(shí)間的延長進(jìn)行性減少。 結(jié)論 2VO術(shù)后8周至12周中,隨著缺血時(shí)間的延長大鼠認(rèn)知進(jìn)行性損害、Numb表達(dá)進(jìn)行性下降。Numb表達(dá)的進(jìn)行性下降可能是慢性缺血導(dǎo)致認(rèn)知功能障礙的重要原因之
[Abstract]:Background and objective with the aging of human society, the incidence of dementia is increasing year by year. Vascular dementia (VD) and Alzheimer's disease (AD) accounted for the majority of dementia in dementia population, and the incidence of VD was slightly higher than that of AD. It brings serious economic and mental burden to the society and the family. In recent years, it is believed that both AD and VD are related to vascular factors. Chronic cerebral ischemia, as a common pathological state of the nervous system, is caused by a variety of causes of chronic cerebral perfusion insufficiency, and resulting in brain metabolic disorders and functional decline. It is a common pathological process in the development of vascular dementia Binswanger disease, Alzheimer's disease, (AD) and other diseases. The role of cerebral blood flow hypoperfusion in the pathogenesis of dementia has become a hot topic. Therefore, it is very important to clarify the pathogenesis of dementia, especially in the condition of chronic cerebral ischemia. Previous studies on cognitive function caused by chronic cerebral ischemia have focused on brain metabolism, cerebral vascular damage, immune cell activity and apoptosis in the brain. Synaptic structure and other aspects. Numb protein was initially found in the development of the peripheral nervous system of Drosophila melanogaster, because of its role in determining cell fate in Drosophila cells, known as cell fate determinant, The same function was found in mammalian and human nervous system, but the structure and function of mammalian Numb protein was more complicated than that of Drosophila. In recent years, Numb has been found to play an important role in neurodevelopment as an endocytosis protein. It is not only involved in regulating asymmetric division of neural precursor cells, maintaining self-renewal of neural progenitor cells, but also in regulating neuronal migration and neuronal growth. The purpose of this study was to explore the relationship between cognitive function and Numb and the possible mechanism of chronic cerebral ischemia by detecting the changes of cognitive function and the dynamic changes of Numb expression in hippocampus of rats with chronic cerebral ischemia. To provide theoretical basis for the study and treatment of cognitive impairment caused by ischemic cerebrovascular disease. Method 1. Forty male Sprague-Dawley rats, aged more than 12 months, were randomly divided into sham-operation group, ischemia 8-week group, ischemic 10-week group and ischemic 12-week group with 10 rats in each group. The model of cerebral perfusion insufficiency (2VO model) was established by permanent ligation of bilateral common carotid artery (2VO model). The remaining treatment in sham-operation group was the same as that in operation group except without ligation of bilateral carotid artery. The Morris water maze test was performed in each group at the corresponding time to detect the learning and memory function of rats. 4. 4. The expression of Numb in rat hippocampal CA1 was detected by immunohistochemistry. 5. 5. The expression of Numb in rat hippocampus was detected by Western bolt. Data acquisition and data analysis. Result 1. The results of behavioral examination showed that the escape latency of ischemic group was significantly longer than that of sham operation group, and the times of crossing the platform were significantly decreased, and with the prolongation of ischemic time, the escape latency was gradually prolonged, and the number of crossing platform was decreased progressively. The results showed that the learning and memory ability of rats after 2VO was obviously impaired, and gradually aggravated with the prolongation of ischemic time. 2. 2. The semi-quantitative immunohistochemical results showed that the expression of Numb in hippocampal CA1 in ischemic group was significantly lower than that in sham-operated group, and gradually decreased with the prolongation of ischemic time. 3.Western bolt results showed that the expression of Numb in hippocampus of ischemic group was significantly lower than that of sham operation group. The expression of Numb in hippocampal CA1 in ischemic group was significantly lower than that in sham operation group, and gradually decreased with the prolongation of ischemic time. Conclusion during the 8-12 weeks after 2VO, the progressive decrease of the expression of numb and the expression of numb may be the important cause of cognitive dysfunction caused by chronic ischemia in rats with progressive cognitive impairment with the prolongation of ischemic time.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R749.1

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相關(guān)碩士學(xué)位論文 前1條

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