本文選題：學(xué)習記憶 + 海馬��； 參考：《長江大學(xué)》2017年碩士論文

【摘要】：背景人口老齡化已成為我國一個非常突出的社會問題。由此帶來的各種動脈粥樣硬化性疾病(尤其是心腦血管疾病)高發(fā)病率已成為嚴重影響我國老年人群健康的頭號問題。腦血管病變引發(fā)的卒中患者數(shù)量日益增多,卒中除引起運動感覺等功能缺失,很大一部分患者還會遺留有程度不同的認知功能障礙。血管性認知障礙(vascular cognitive impairment,VCI)臨床癥狀表現(xiàn)為學(xué)習記憶能力受損的的障礙性疾病,嚴重者可進展為血管性癡呆。認知障礙造成患者生活自理能力明顯下降,給家庭社會帶來很大的負擔。癡呆已經(jīng)成為一個越來越嚴重的全球性公共衛(wèi)生問題,受到各國神經(jīng)病學(xué)研究人員和政府的重視。目前治療中仍無特效的藥物和治療手段。如何改善認知功能問題已成為腦科學(xué)的重要研究課題。重復(fù)經(jīng)顱磁刺激(repetitive transcranial magnetic stimulation,rTMS)是近年逐漸應(yīng)用于臨床的一種影響和改變大腦功能的磁刺激技術(shù),治療效果在多種神經(jīng)精神疾病的治療中得到了肯定。但在對認知功能障礙的改善上的影響研究相對較少,作用機制不清。認知是人腦特有的高級功能。腦結(jié)構(gòu)中與學(xué)習記憶最密切的腦區(qū)是海馬。中樞神經(jīng)元的突觸可塑性決定著學(xué)習記憶功能。長時程增強(long-term potentiation,LTP)現(xiàn)象是中樞神經(jīng)突觸可塑性的重要形式和指標。VCI模型大鼠為實驗研究對象,Morris水迷宮進行動物行為學(xué)實驗,電生理學(xué)實驗觀察海馬突觸功能可塑性,從宏觀和微觀兩角度觀察低頻重復(fù)經(jīng)顱磁刺激對VCI大鼠學(xué)習和大鼠腦海馬區(qū)長時程增強現(xiàn)象的影響。目的研究低頻重復(fù)經(jīng)顱磁刺激對血管性認知障礙大鼠認知功能的影響,探討低頻經(jīng)顱磁刺激治療對血管性認知障礙大鼠的認知影響和細胞水平的分子機制,為磁刺激治療血管性認知障礙提供理論依據(jù),豐富治療手段。方法實驗動物2個月齡大雄性SD大鼠75只,隨機等分為正常組、假手術(shù)組、模型組、rTMS刺激組四組(造模成功后每組為15只)。VCI模型大鼠制備采用間斷夾閉雙側(cè)頸總動脈伴低血壓法。Morris水迷宮通過逃避潛伏期和穿越平臺次數(shù)測試進行動物行為學(xué)實驗。電生理學(xué)實驗采用電生理技術(shù)記錄胞外刺激誘發(fā)的海馬區(qū)群峰電位的變化率為對照指標,并觀察海馬區(qū)突觸長時程增強(LTP)形成情況。步驟為制備含海馬的大鼠腦片,置于灌流有95%O2+5%CO2混合氣體與人工腦脊液的灌流槽內(nèi)。腦片海馬前穿通纖維區(qū)放置刺激電極,齒狀回放置記錄電極,DS3電子刺激器產(chǎn)生誘發(fā)電刺激群峰電位顯示于示波器上,Spike2數(shù)據(jù)分析軟件分析。以各時間點的群峰電位變化幅值與基礎(chǔ)幅值比較所得出的相對百分比(%)作為結(jié)果記錄并觀察LTP形成的現(xiàn)象。統(tǒng)計學(xué)分析數(shù)據(jù)統(tǒng)計分析采用SPSS19.0軟件,水迷宮結(jié)果及海馬突觸區(qū)群峰電位(PS)變化幅值與基礎(chǔ)幅值比較的百分率等計量資料以均數(shù)±標準差(?x士s)表示。組間比較采用One way NAOVA分析,P0.05認定結(jié)果有統(tǒng)計學(xué)意義。結(jié)果假手術(shù)組大鼠與正常組大鼠比較差異無統(tǒng)計學(xué)意義,單純手術(shù)操作不會加重大鼠認知功能障礙。VCI模型大鼠學(xué)習記憶能力與正常大鼠比較明顯下降。Morris水迷宮實驗VCI大鼠定位巡航、穿越平臺能力下降,離體存活腦片海馬齒狀回區(qū)LTP減弱。低頻rTMS刺激VCI模型大鼠后可改善模型大鼠學(xué)習記憶能力,表現(xiàn)為模型大鼠定位巡航實驗,空間探索實驗?zāi)芰υ鰪?海馬區(qū)LTP現(xiàn)象增加。實驗中未見實驗鼠不良反應(yīng),各組大鼠均耐受性良好,低頻rTMS治療安全有效。結(jié)論rTMS可能因增強VCI模型大鼠海馬區(qū)突觸的功能可塑性而安全有效地改善VCI模型大鼠的學(xué)習記憶認知功能。
[Abstract]:The aging of the population has become a very prominent social problem in China. The high incidence of all kinds of atherosclerotic diseases, especially the cardiovascular and cerebrovascular diseases, has become the first problem that seriously affects the health of the elderly in our country. The number of stroke patients caused by cerebrovascular disease is increasing, and the stroke causes a sense of movement. A large part of the patients will still have a different cognitive impairment. The clinical symptoms of vascular cognitive impairment (VCI) are manifested by impaired learning and memory impairment, and the serious people can develop into a vascular idiot. Cognitive impairment leads to the patient's self-care ability. The decline has brought a great burden to the family society. Dementia has become a more and more serious global public health problem. It has been paid much attention by neurology researchers and government in various countries. There are still no special drugs and treatments in the treatment. How to improve cognitive function has become an important research topic in brain science. Repetitive transcranial magnetic stimulation (rTMS) is a magnetic stimulation technique that has been gradually applied to the clinic in recent years to influence and change the function of the brain. The therapeutic effect has been confirmed in the treatment of many neuropsychiatric disorders. However, the effect on the improvement of cognitive impairment is relatively less and the mechanism of action is relatively less. Not clear. Cognition is a unique advanced function of the human brain. The brain region which is most closely related to learning and memory is the hippocampus. The synaptic plasticity of the central neurons determines the learning and memory function. The long-term potentiation (LTP) phenomenon is an important form and index of the plasticity of the central nervous synapse. The rat model of the.VCI model is the experimental study of the experimental study. Elephant, Morris water maze conducted animal behavior experiments and electrophysiological experiments to observe the plasticity of hippocampal synaptic function. The effects of low-frequency repetitive transcranial magnetic stimulation on the long Shi Cheng enhancement phenomenon in VCI rats and rat hippocampus were observed from the macroscopic and microscopic two angles. Objective to study the effects of low frequency repetitive transcranial magnetic stimulation on vascular cognitive impairment rats The effect of cognitive function on the cognitive effects of low frequency transcranial magnetic stimulation therapy on cognitive impairment in rats and the molecular mechanism of cell level, providing a theoretical basis for the treatment of vascular cognitive impairment by magnetic stimulation, and enriching the treatment methods. Methods 75 rats of 2 months old male SD rats were randomly divided into normal group and sham operation group. Model group, four groups of rTMS stimulation group (15 rats in each group after model success).VCI model rats were prepared by intermittent clamping of the bilateral common carotid artery and hypotension in.Morris water maze. The experiment of animal behavior was carried out by the escape latency and the number of crossing platform times. Electrophysiological experiments used electrophysiological techniques to record the hippocampus induced by extracellular stimulation. The change rate of the peak potential of the region was the control index, and the formation of the synaptic long time potentiation (LTP) in the hippocampus was observed. The step was to prepare the rat brain slices containing the hippocampus in the perfusion slot with 95%O2+5%CO2 mixed gas and artificial cerebrospinal fluid. The stimulation electrode was placed in the anterior hippocampus of the brain slices, the recording electrode was placed in the dentate gyrus, and the DS3 electron was placed. The stimulator generated the generation of generating electricity to stimulate the peak potential of the peak potential on the oscilloscope, Spike2 data analysis software analysis. The relative percentage (%) of the peak potential change amplitude compared with the basic amplitude at each time point is recorded and observed the phenomenon of LTP formation. Statistical analysis of statistical analysis uses SPSS19.0 software, water maze. Results and the percentage of peak potential (PS) changes in the hippocampal synapse region and the percentage of basic amplitude compared with the basic amplitude (? X s). Compared with the One way NAOVA analysis, the results of P0.05 identification were statistically significant. The results showed that there was no statistically significant difference between the rats in the sham operation group and the normal group, and the simple surgical operation was not significant. The ability of learning and memory in.VCI model rats was significantly lower than that of normal rats..Morris water maze test of VCI rats was located on cruise, the ability to cross the platform decreased, and the LTP in the hippocampal dentate gyrus of the isolated surviving brain slices decreased. The low frequency rTMS stimulated the learning and memory ability of the model rats after the stimulation of the VCI model. This is the model rat positioning cruise experiment. The ability of space exploration and experiment is enhanced and the LTP phenomenon in the hippocampus is increased. There is no adverse reaction in the experimental rats. The rats in each group are well tolerated and the low frequency rTMS is safe and effective. Conclusion rTMS may improve the function plasticity of the synapse in the hippocampus of the VCI model rats and improve the VCI model safely and effectively. The cognitive function of learning and memory in rats.

【學(xué)位授予單位】：長江大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R749.13

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