本文選題：抑郁癥 + 海馬　； 參考：《新鄉(xiāng)醫(yī)學(xué)院》2013年碩士論文

【摘要】：背景 抑郁癥是一種以心境低落為主要特征的慢性反復(fù)發(fā)作性疾病,嚴(yán)重影響著全球約20%人群的身心健康以及生活質(zhì)量。目前抑郁癥的發(fā)生機(jī)制尚不明確。近年來,海馬神經(jīng)可塑性的研究成為抑郁癥發(fā)病機(jī)制研究的熱點之一。同時,突觸后致密蛋白-95(postsynaptic density protein-95, PSD-95)是位于突觸后特化區(qū)內(nèi)的主要支架蛋白,在調(diào)控神經(jīng)突觸發(fā)育和可塑性中起關(guān)鍵作用,并參與學(xué)習(xí)記憶等功能的調(diào)節(jié)。課題擬通過研究抑郁模型大鼠海馬區(qū)PSD-95的表達(dá)和神經(jīng)元細(xì)胞結(jié)構(gòu)在藥物干預(yù)下的改變,從而探討抑郁癥可能的發(fā)病機(jī)制。 目的 1.探討抑郁模型大鼠學(xué)習(xí)記憶能力變化及藥物干預(yù)的影響。 2.探討抑郁模型大鼠海馬神經(jīng)元形態(tài)變化以及藥物干預(yù)的改變。 3.探討抑郁模型大鼠海馬各區(qū)PSD-95表達(dá)水平及藥物干預(yù)對其影響。 4.探討抑郁模型大鼠海馬各區(qū)PSD-95蛋白表達(dá)水平與學(xué)習(xí)記憶能力之間的關(guān)系。 方法 1.大鼠先分為正常對照組(n=16)和造模組(n=48)。造模組建立慢性不可預(yù)見應(yīng)激(chronic unpredictable stress, CUS)抑郁模型,再將造模組分為三組：抑郁模型組(n=16,不進(jìn)行灌胃操作)、生理鹽水組(n=16,每日灌胃注入生理鹽水)和藥物干預(yù)組(n=16,每日灌胃注入舍曲林)。 2.通過測量體重、蔗糖水消耗試驗和曠場試驗檢測大鼠的行為學(xué)變化,通過Y迷宮檢測大鼠的學(xué)習(xí)記憶等認(rèn)知功能。 3.采用HE染色法觀察大鼠海馬區(qū)神經(jīng)元錐體、顆粒細(xì)胞形態(tài)結(jié)構(gòu)。 4.采用免疫組化方法檢測四組大鼠海馬區(qū)PSD-95蛋白表達(dá)水平；運(yùn)用逆轉(zhuǎn)錄聚合酶鏈反應(yīng)(RT-PCR)法檢測海馬區(qū)PSD-95mRNA的表達(dá)水平。 5.采用相關(guān)分析法分析藥物干預(yù)后四組大鼠海馬各區(qū)PSD-95蛋白表達(dá)水平與學(xué)習(xí)記憶能力之間的關(guān)系。 結(jié)果 1.造模前后及藥物干預(yù)后結(jié)果：大鼠造模前在體重(t=1.967,P0.05)、蔗糖水消耗(t=1.352,P0.05)、曠場試驗中央停留時間(t=0.073,P0.05),水平運(yùn)動距離(t=-0.184,P0.05)、豎立次數(shù)(t=-0.396,P0.05),Y迷宮試驗錯誤反應(yīng)次數(shù)(t=-0.404,P0.05),正確反應(yīng)次數(shù)(t=-0.805,P0.05),總潛伏期時間(t=-0.455,P0.05)差異均無統(tǒng)計學(xué)意義,提示可進(jìn)行CUS模型建立。 造模后在體重(t=18.909,P0.05)、蔗糖水消耗(t=-20.414,P0.05)、曠場試驗中央停留時間(t=-10.420,P0.05)、水平運(yùn)動距離(t=-11.859,P0.05)、豎立次數(shù)(t=14.060,P0.05),Y迷宮試驗錯誤反應(yīng)次數(shù)(t=--6.140,P0.05),正確反應(yīng)次數(shù)(t=8.28,P0.05),總潛伏期時間(t=-17.66,P0.05)差異有統(tǒng)計學(xué)意義,證明抑郁模型建立成功。 藥物干預(yù)結(jié)束后,四組大鼠行為學(xué)評分比較：體重(F=454.279,P0.05),蔗糖水消耗(F=172.896,P0.05),曠場試驗中央停留時間(F=246.178,P0.05),水平運(yùn)動距離(F=430.354,P0.05),豎立次數(shù)(F=1354.272,P0.05),Y迷宮試驗錯誤反應(yīng)次數(shù)(F=23.150,P0.05),正確反應(yīng)次數(shù)(F=40.258,P0.05),總潛伏期時間(F=129.083,P0.05)差異均具有統(tǒng)計學(xué)意義,顯示抑郁模型大鼠各項行為學(xué)指標(biāo)降低且空間學(xué)習(xí)、記憶提取與保持能力下降,藥物干預(yù)可改善抑郁狀態(tài)以及學(xué)習(xí)記憶能力。 2.HE染色結(jié)果：抑郁模型大鼠海馬區(qū)神經(jīng)元細(xì)胞形態(tài)結(jié)構(gòu)發(fā)生病理性改變；通過藥物干預(yù)可使其改善。四組大鼠海馬區(qū)神經(jīng)元錐體、顆粒細(xì)胞數(shù)目(FCA1=8.228,P0.05；FCA3=34.143,P0.05；FDG=275.035,P0.05),神經(jīng)元錐體、顆粒細(xì)胞灰度值(FCA1=88.494,P0.05；FCA3=89.398,P0.05；FDG=236.085,P0.05),差異有統(tǒng)計學(xué)意義。 3.免疫組化結(jié)果：四組大鼠海馬區(qū)PSD-95蛋白陽性細(xì)胞數(shù)目(FCA1=16.497,P0.05；FCA3=23.494,P0.01；FDG=37.628,P0.05),陽性細(xì)胞積分光密度(FCA1=26.659,P0.05；FCA3=13.556,P0.05；FDG=6.158,P0.05),差異有統(tǒng)計學(xué)意義,顯示PSD-95表達(dá)水平不同。 4. RT-PCR結(jié)果：四組大鼠海馬區(qū)PSD-95mRNA表達(dá)情況比較(F=290.951,P0.05),其中抑郁模型大鼠表達(dá)水平低于正常組(P0.05),藥物干預(yù)組大鼠表達(dá)水平高于抑郁模型大鼠(P0.05),差異具有統(tǒng)計學(xué)意義。其余各組比較差異無統(tǒng)計學(xué)意義。 5. Pearson相關(guān)性分析結(jié)果：四組大鼠海馬CA1區(qū)、CA3區(qū)和DG區(qū)PSD-95陽性細(xì)胞數(shù)目與Y迷宮各參數(shù)相關(guān)性分析,其中抑郁模型大鼠海馬CA1區(qū)PSD-95陽性細(xì)胞數(shù)目與錯誤反應(yīng)次數(shù)呈負(fù)相關(guān)(r=-0.769,P0.05)、與總逃避潛伏期呈負(fù)相關(guān)(r=0.800,P0.05)、與正確反應(yīng)次數(shù)呈正相關(guān)(r=0.800,P0.05),抑郁模型大鼠海馬CA3區(qū)PSD-95陽性細(xì)胞數(shù)目與錯誤反應(yīng)次數(shù)呈負(fù)相關(guān)(r=-0.751,P0.05)、與總逃避潛伏期呈負(fù)相關(guān)(r=-0.832,P0.05)、與正確反應(yīng)次數(shù)呈正相關(guān)(r=0.862,P0.05),抑郁模型大鼠海馬DG區(qū)PSD-95陽性細(xì)胞數(shù)目與錯誤反應(yīng)次數(shù)呈負(fù)相關(guān)(r=-0.699,P0.05)、與總逃避潛伏期時間呈負(fù)相關(guān)(r=-0.869,P0.05)、與正確反應(yīng)次數(shù)呈正相關(guān)(r=0.728,P0.05)。 結(jié)論 1.抑郁癥中海馬神經(jīng)可塑性參與情緒、學(xué)習(xí)記憶功能的調(diào)節(jié),海馬神經(jīng)元細(xì)胞形態(tài)結(jié)構(gòu)及數(shù)量的改變可能是神經(jīng)可塑性及抑郁癥發(fā)生的形態(tài)學(xué)基礎(chǔ)。 2.舍曲林能改善抑郁模型大鼠的學(xué)習(xí)記憶認(rèn)知功能并逆轉(zhuǎn)海馬內(nèi)PSD-95低表達(dá)以及神經(jīng)元細(xì)胞形態(tài)結(jié)構(gòu)病理可塑性改變,可能是舍曲林抗抑郁機(jī)制作用之一。
[Abstract]:background
Depression is a chronic and recurrent disease characterized by depression, which seriously affects the physical and mental health and quality of life of about 20% people around the world. The mechanism of depression is not yet clear. In recent years, the study of hippocampal plasticity has become one of the hotspots in the study of the pathogenesis of depression. -95 (postsynaptic density protein-95, PSD-95) is the main scaffold protein in the postsynaptic special area. It plays a key role in regulating the development and plasticity of synapse, and participates in the regulation of learning and memory. The topic is to study the expression of PSD-95 in the hippocampus of the depressive model rats and the neuron cell structure in the drug. Interventions to explore possible mechanisms of depression.
objective
1. to explore the changes of learning and memory ability and the effect of drug intervention in depression model rats.
2. to explore the morphological changes of hippocampal neurons in rats with depression and the changes of drug intervention.
3. to investigate the expression level of PSD-95 in hippocampus of depression model rats and the effect of drug intervention.
4. to explore the relationship between PSD-95 protein expression and learning and memory ability in hippocampus of depression model rats.
Method
The 1. rats were first divided into normal control group (n=16) and model group (n=48). The model of chronic unforeseeable stress (chronic unpredictable stress, CUS) depression model was established, and then the model group was divided into three groups: depression model group (n=16, no gastric perfusion), saline group (n=16, daily intragastric injection of saline) and drug intervention group (n=16, each) Daily intragastric injection of sertraline.
2. by measuring body weight, sucrose water consumption test and open field test, the behavioral changes of rats were detected, and the learning and memory functions of rats were detected by Y maze.
3. HE staining was used to observe the pyramidal structure and granule cell morphology of hippocampal neurons in rats.
4. the expression level of PSD-95 protein in the hippocampus of four rats was detected by immunohistochemical method, and the expression level of PSD-95mRNA in the hippocampus was detected by reverse transcription polymerase chain reaction (RT-PCR).
5. correlation analysis was used to analyze the relationship between PSD-95 protein expression and learning and memory ability in four groups of hippocampus after drug intervention.
Result
1. before and after modeling and after the drug intervention: the body weight (t=1.967, P0.05), sucrose water consumption (t=1.352, P0.05), t=0.073 (P0.05), t=-0.184, P0.05, t=-0.396, P0.05, Y labyrinth test. 0.05) the total latency time (t=-0.455, P0.05) was not statistically significant, suggesting that CUS model could be established.
After the model, the body weight (t=18.909, P0.05), the sucrose water consumption (t=-20.414, P0.05), the central residence time (t=-10.420, P0.05) in the open field test, the horizontal movement distance (t=-11.859, P0.05), the vertical number of times (t=14.060, P0.05), the false reaction times of Y labyrinth test, the correct response times, the total latency time. The difference was statistically significant, demonstrating the success of the depression model.
After the drug intervention, the four groups of rats' behavioral score were compared: weight (F=454.279, P0.05), sucrose water consumption (F=172.896, P0.05), central stay time (F=246.178, P0.05) in open field test, horizontal movement distance (F=430.354, P0.05), vertical frequency (F= 1354.272, P0.05), Y labyrinth test error times (F=23.150, P0.05), and the correct response times 40.258, P0.05), the difference in total latency time (F=129.083, P0.05) was statistically significant, which showed that the behavioral indexes of the depression model rats were reduced and the spatial learning, the ability of memory extraction and retention decreased, and the drug intervention could improve the state of depression and the learning and memory ability.
2.HE staining results: the morphological and structural changes of neurons in the hippocampus of the depression model rats were histopathologically altered. The pyramids of the neurons in the hippocampus of the four groups of rats, the number of granular cells (FCA1=8.228, P0.05; FCA3=34.143, P0.05; FDG=275.035, P0.05), the pyramids of the neurons, the gray value of granular cells (FCA1=88.494, P0.0) 5; FCA3=89.398, P0.05; FDG=236.085, P0.05), the difference was statistically significant.
3. the results of immunohistochemistry: the number of PSD-95 protein positive cells in the hippocampus of four rats (FCA1=16.497, P0.05; FCA3=23.494, P0.01; FDG=37.628, P0.05), the integral light density of positive cells (FCA1=26.659, P0.05; FCA3=13.556, P0.05; FDG=6.158,), which showed that the expression level was different.
4. RT-PCR results: the expression of PSD-95mRNA in the hippocampus of the four rats was compared (F=290.951, P0.05), in which the expression level of the depression model rats was lower than that of the normal group (P0.05). The expression level of the rats in the drug intervention group was higher than that of the depression model rats (P0.05), the difference was statistically significant. The other groups had no statistical significance.
5. Pearson correlation analysis: the correlation between the number of PSD-95 positive cells in the hippocampal CA1, CA3 and DG areas in the hippocampus of the four rats was correlated with the parameters of the Y maze, in which the number of PSD-95 positive cells in the hippocampus CA1 region was negatively correlated with the number of false reactions (r=-0.769, P0.05), and was negatively correlated with the total escape latency (r=0.800, P0.05), and positive. The number of positive responses was positively correlated (r=0.800, P0.05). The number of PSD-95 positive cells in the hippocampus CA3 area of the depression model rats was negatively correlated with the number of wrong responses (r=-0.751, P0.05), which was negatively correlated with the total escape latency (r=-0.832, P0.05), and was positively correlated with the number of correct responses (r=0.862, P0.05), and the number of PSD-95 positive cells in the hippocampus DG region of the depressive model rats. There was a negative correlation with the number of errors (r=-0.699, P0.05), which was negatively correlated with the total escape latency time (r=-0.869, P0.05), and had a positive correlation with the number of correct responses (r=0.728, P0.05).
conclusion
1. the plasticity of hippocampus nerve plasticity participates in emotion, learning and memory function is regulated, the morphological structure and quantity of hippocampal neurons may be the morphological basis of nerve plasticity and depression.
2. sertraline can improve the cognitive function of learning and memory in the depression model rats and reverse the low expression of PSD-95 in the hippocampus and the morphological and pathological changes in the morphological structure of neurons. It may be one of the antidepressant mechanisms of sertraline.

【學(xué)位授予單位】：新鄉(xiāng)醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R749.4;R-332

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