本文選題：甲狀腺素受體α1 + 阿爾茨海默病�。� 參考：《蘭州大學(xué)》2012年碩士論文

【摘要】：目的：復(fù)制阿爾茨海默病動(dòng)物模型,觀察其大腦皮層和海馬區(qū)腦組織中甲狀腺素受體THR α1的表達(dá)與阿爾茨海默病發(fā)生的相關(guān)性,并從THRα1表達(dá)增加對(duì)神經(jīng)細(xì)胞tau蛋白磷酸化影響的角度對(duì)其機(jī)制進(jìn)行初步探討。 方法：SD大鼠腹腔注射D-半乳糖50mg·kg-1·d-1,復(fù)制阿爾茨海默病動(dòng)物模型,另設(shè)正常對(duì)照組,腹腔注射等量生理鹽水。連續(xù)給藥6w后觀察觀察動(dòng)物一般情況如精神狀態(tài)、活動(dòng)情況、皮毛等；經(jīng)二次固定法固定后取全腦組織制作病理切片,進(jìn)行HE染色和改良Bicschowsky染色,用以觀察大腦皮層及海馬組織中老年斑,神經(jīng)元纖維纏結(jié)及神經(jīng)元數(shù)量、體積、排列狀況等形態(tài)學(xué)變化；分別用實(shí)時(shí)熒光定量PCR (Real time fluorescence quantitation PCR, FQ-PCR)法和Western blot法檢測(cè)阿爾茨海默病動(dòng)物與正常大鼠腦組織中THRα1、CDK-5及p35mRNA的差異性表達(dá)和pser404-tau蛋白的表達(dá)水平。 結(jié)果：與正常對(duì)照組相比,阿爾茨海默病模型組動(dòng)物神情呆滯，反應(yīng)遲鈍,撮毛等；鏡下見(jiàn)大腦皮層及海馬區(qū)神經(jīng)元排列紊亂、層次減少,核呈固縮、深染狀,神經(jīng)元軸突染色較深呈拖尾狀,形成神經(jīng)元纖維纏結(jié),尤以海馬區(qū)表現(xiàn)更為顯著。與對(duì)照組相比,模型組皮層區(qū)THRα1、CDK-5和p35mRNA表達(dá)量增加,分別為1.20±0.30、4.71±0.54、2.11±0.40,差異有統(tǒng)計(jì)學(xué)意義(P0.05)；模型組海馬區(qū)三者的表達(dá)量分別為2.53±0.65、18.51±2.77、5.96±0.49,與對(duì)照組相比亦有統(tǒng)計(jì)學(xué)差異(P0.05)模型組pser404-tau蛋白呈高表達(dá)狀態(tài),與正常對(duì)照組相比P0.05。 結(jié)論：阿爾茨海默病動(dòng)物大腦皮層及海馬區(qū)神經(jīng)細(xì)胞中THRα1mRNA的表達(dá)量顯著高于正常對(duì)照組大鼠,過(guò)高THRα1可提高tau蛋白磷酸化相關(guān)激酶CDK-5mRNA及其調(diào)節(jié)因子p35mRNA的表達(dá)水平,進(jìn)而加劇神經(jīng)細(xì)胞tau蛋白磷酸化,導(dǎo)致動(dòng)物大腦皮層及海馬區(qū)出現(xiàn)神經(jīng)元丟失、神經(jīng)纖維纏結(jié)等典型的AD形態(tài)學(xué)變化,這可能是THRα1過(guò)表達(dá)導(dǎo)致阿爾茨海默病發(fā)生的主要機(jī)制之一。
[Abstract]:Objective: to study the relationship between the expression of thyroxine receptor THR 偽 1 in cerebral cortex and hippocampus and the occurrence of Alzheimer's disease.The effect of THR 偽 1 expression on the phosphorylation of tau protein in nerve cells was also discussed.Methods Dgalactose 50mg kg-1 d-1 was injected intraperitoneally to make Alzheimer's disease animal model. The normal control group was set up and the same amount of normal saline was injected intraperitoneally.After 6 weeks of continuous administration, the general conditions of animals, such as mental state, activity, fur and so on, were observed, and the whole brain tissue was fixed by two fixation methods to make pathological sections for HE staining and modified Bicschowsky staining.To observe the morphological changes of senile plaques, the number, volume and arrangement of neurons in cerebral cortex and hippocampal tissue.Real time fluorescence quantitation PCR (FQ-PCR) and Western blot were used to detect the differential expression of THR 偽 1 CDK-5 and p35mRNA and the expression of pser404-tau protein in brain tissue of Alzheimer's disease and normal rats, respectively.Results: compared with the normal control group, the Alzheimer's disease model group showed dull expression, slow response, hair and so on, and the neurons of cerebral cortex and hippocampus were disordered, the layers decreased, the nucleus was pyknotic, deep stained, and so on.The axon staining of the neurons was deeply trailing, forming the neuronal fibrillary tangles, especially in the hippocampal area.Compared with the control group, the expression of THR 偽 1, CDK-5 and p35mRNA in the cortical area of the model group was increased.The expression of pser404-tau protein in the hippocampal area of the model group was 2.53 鹵0.65 鹵2.775 鹵0.49, respectively, which was significantly higher than that in the control group (P 0.05) and the expression of pser404-tau protein in the model group was significantly higher than that in the normal control group (P 0.05). The expression of pser404-tau protein in the model group was significantly higher than that in the control group (P 0.05), and that in the hippocampal area of the model group was 2.53 鹵0.65 鹵2.775 鹵0.49, which was also significantly higher than that in the control group (P 0.05).Conclusion: the expression of THR 偽 1mRNA in cerebral cortex and hippocampal neurons of Alzheimer's disease rats is significantly higher than that in normal control rats. Excessive THR 偽 1 can increase the expression of tau protein phosphorylated kinase CDK-5mRNA and its regulatory factor p35mRNA.In turn, the phosphorylation of tau protein in nerve cells is aggravated, resulting in the loss of neurons and neuronal tangles in the cortex and hippocampus of animals, and typical AD morphological changes, such as neurofibrillary tangles, and so on.This may be one of the main mechanisms of overexpression of THR 偽 1 leading to Alzheimer's disease.
【學(xué)位授予單位】：蘭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類(lèi)號(hào)】：R749.16

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