本文選題：鋁 + AMPA受體�。� 參考：《山西醫(yī)科大學(xué)》2013年碩士論文

【摘要】：[目的]通過對大鼠亞慢性染鋁,建立學(xué)習(xí)記憶損傷模型,觀察AMPA受體在鋁致大鼠學(xué)習(xí)記憶損傷中的可能作用。 [方法] 1、建立動物染鋁模型：健康雄性剛成年SD大鼠36只,按體重隨機(jī)分為：0.41mg/kg-bw、0.82mg/kg·bw、1.23mg/kg-bw麥芽酚鋁[Al(mal)3]組和對照組(生理鹽水),腹腔注射染毒8周。 2、采用石墨爐原子吸收分光光度法測定大鼠腦中鋁含量。 3、采用Morris水迷宮試驗(yàn)進(jìn)行大鼠學(xué)習(xí)記憶能力檢測,其中定位導(dǎo)航試驗(yàn)檢測大鼠空間學(xué)習(xí)能力,空間探索實(shí)驗(yàn)檢測大鼠的空間記憶能力。 4、采用HE染色法觀察大鼠海馬區(qū)病理組織學(xué)變化。 5、采用實(shí)時(shí)熒光定量PCR法檢測AMPA受體各亞單位GluRl,GluR2,GluR3基因表達(dá)情況。 6、采用免疫組化和Western blot法檢測大鼠腦組織中AMPA受體亞單位GluR1, GluR2, GluR3的蛋白表達(dá)水平。 [結(jié)果] 1、隨著染鋁劑量的增加,染鋁組大鼠腦鋁含量也逐漸增加,并且其余各組與對照組相比,差別有統(tǒng)計(jì)學(xué)意義(P0.05)。 2、大鼠學(xué)習(xí)記憶能力測試結(jié)果表明與對照組相比,中、高劑量組大鼠找到平臺時(shí)間明顯延長(P0.05,P0.05)。中、高劑量組在目標(biāo)象限停留時(shí)間與對照組相比都明顯減少(P0.05,P0.05),高劑量組穿越平臺次數(shù)與對照組相比明顯減少(P0.05)。 3、HE染色結(jié)果表明隨著鋁劑量的增加,大鼠海馬組織錐體層細(xì)胞排列分散,細(xì)胞數(shù)目減少,出現(xiàn)核固縮、空泡變性等病理改變。 4、實(shí)時(shí)熒光定量PCR法結(jié)果表明隨著染鋁劑量的增加,大鼠海馬內(nèi)的AMrA受體各亞基GluRl,GluR2,GluR3基因表達(dá)下降,低、中、高劑量組的基因表達(dá)較對照組均顯著降低(P0.01,P0.01,P0.05)。 5、免疫組化法結(jié)果發(fā)現(xiàn)不同劑量組大鼠海馬區(qū)可見不同程度的棕黃色深染顆粒(陽性表達(dá)),并且隨著染鋁劑量的增加,陽性表達(dá)越來越少。G1uRl低、中、高劑量組與對照組相比表達(dá)下降(P0.01)；G1uR2的低、中、高劑量組與對照組相比,陽性表達(dá)也逐漸下降(P0.01)；G1uR3蛋白表達(dá)也有所下降,但各染鋁劑量組與對照組相比沒有統(tǒng)計(jì)學(xué)意義。Westem b10t法結(jié)果表明AMPA受體各亞基蛋白水平隨著染鋁劑量的增加而呈逐漸下降趨勢。GluRl的中、高劑量組蛋白表達(dá)較對照組均顯著降低(P0.01)；G1uR2的蛋白表達(dá)呈下降趨勢,高劑量組的蛋白表達(dá)較對照組顯著降低(P0.01)；G1uR3蛋白表達(dá)呈下降趨勢,但各染鋁劑量組與對照組相比沒有統(tǒng)計(jì)學(xué)意義。 [結(jié)論] 亞慢性染鋁后,大鼠腦內(nèi)鋁含量表達(dá)升高,學(xué)習(xí)記憶能力下降,腦內(nèi)海馬區(qū)細(xì)胞形態(tài)發(fā)生變化。在此過程中,也觀察到海馬AMPA受體亞單位在基因和蛋白水平表達(dá)下降,提示AMPA受體表達(dá)下降可能是鋁致大鼠學(xué)習(xí)記憶損傷的作用機(jī)制之一。
[Abstract]:[Objective] to establish a learning and memory impairment model by subchronic aluminum exposure in rats and observe the possible role of AMPA receptor in learning and memory impairment induced by aluminum.
[method]
1, an animal model of aluminum dye was established: 36 healthy male adult SD rats were randomly divided into 0.41mg/kg-bw, 0.82mg/kg / BW, 1.23mg/kg-bw maltol aluminum [Al (mal) 3] group and control group (physiological saline) and intraperitoneal injection for 8 weeks.
2, the content of aluminum in rat brain was determined by graphite furnace atomic absorption spectrometry.
3, the Morris water maze test was used to test the learning and memory ability of rats, in which the spatial learning ability of rats was detected by positioning navigation test, and spatial memory ability of rats was detected by space exploration experiment.
4, HE staining was used to observe histopathological changes in the hippocampus of rats.
5, real-time fluorescence quantitative PCR was used to detect the expression of AMPA receptor subunits GluRl, GluR2 and GluR3 genes.
6, immunohistochemistry and Western blot were used to detect the protein expression level of AMPA receptor subunit GluR1, GluR2 and GluR3 in rat brain.
[results]
1, as the dose of aluminum increased, the aluminum content in the brain of the rats exposed to aluminum increased gradually, and there was a significant difference between the other groups and the control group (P0.05).
2, the test results of learning and memory ability of rats showed that compared with the control group, the time of finding the platform in the high dose group was significantly longer (P0.05, P0.05). In the high dose group, the stay time in the target quadrant was significantly reduced (P0.05, P0.05), and the number of high dose group crossing platform decreased significantly compared with the control group (P0.05).
3, the results of HE staining showed that with the increase of aluminum dose, the pyramidal cells in the hippocampus of the rat were arranged and dispersed, the number of cells decreased, and the nuclear pyknosis, vacuolation and other pathological changes appeared.
4, the results of real time fluorescence quantitative PCR showed that the expression of GluRl, GluR2, GluR3 gene of AMrA receptor in hippocampus of rats decreased with the increase of dose of aluminum dye, and the expression of gene expression in high dose group decreased significantly (P0.01, P0.01, P0.05) in the high dose group.
5, the results of immunohistochemical staining found that the hippocampus of the rats in different doses was found to have different degrees of brown and yellow deep stained particles (positive expression), and with the increase of the dose of aluminum, the positive expression was less and less.G1uRl, the high dose group was lower than the control group (P0.01), and the low, middle and high dose group of G1uR2 was positive expression compared with the control group. It also decreased (P0.01), and the expression of G1uR3 protein decreased, but there was no statistical significance between the dosage group and the control group..Westem b10t method showed that the level of AMPA receptor subunit protein decreased gradually in.GluRl with the increase of aluminum dose, and the expression of high dose histone was significantly lower than that of the control group (P0.01). The protein expression of G1uR2 decreased significantly, the expression of protein in high dose group was significantly lower than that in the control group (P0.01), and the expression of G1uR3 protein showed a declining trend, but there was no statistical significance in the dosage group of all aluminum dyes compared with the control group.
[Conclusion]
After subchronic aluminum staining, the expression of aluminum content in the brain of rats increased, the ability of learning and memory decreased and the cell morphology of the hippocampus in the brain changed. In this process, the expression of AMPA receptor subunit in the hippocampus decreased at the level of gene and protein, suggesting that the decline of AMPA receptor expression may be one of the mechanisms of learning and memory impairment in rats.

【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R114

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 王亞鵬;董奇;;腦的可塑性研究:現(xiàn)狀與進(jìn)展[J];北京師范大學(xué)學(xué)報(bào)(社會科學(xué)版);2007年03期

2 劉祚周;海馬結(jié)構(gòu)在學(xué)習(xí)記憶和痛覺調(diào)制中的功能——電生理及神經(jīng)化學(xué)研究[J];第三軍醫(yī)大學(xué)學(xué)報(bào);2003年03期

3 申冬杰,趙先英;鋁與人體健康[J];國外醫(yī)學(xué)(醫(yī)學(xué)地理分冊);2004年02期

4 李增禧,樓蔓藤,李小j,梁業(yè)成,盛少禹;鋁對人類智能的損害及其對策的研究[J];廣東微量元素科學(xué);2000年04期

5 尹學(xué)鈞;董蒼榮;劉君卓;;鋁的腦轉(zhuǎn)運(yùn)及其對血腦屏障功能的影響[J];國外醫(yī)學(xué)(衛(wèi)生學(xué)分冊);1996年04期

6 傅洪軍;鋁的神經(jīng)毒性與老年性癡呆的研究進(jìn)展[J];國外醫(yī)學(xué)(衛(wèi)生學(xué)分冊);2001年06期

7 李紅彥;劉萍;徐華雷;張雅楠;鞏泉泉;;鋁螯合劑對鋁染毒大鼠學(xué)習(xí)記憶及興奮性氨基酸類神經(jīng)遞質(zhì)的影響[J];環(huán)境與健康雜志;2008年11期

8 柯尊記,姚志彬;空間學(xué)習(xí)記憶的行為模式及其分子神經(jīng)生物學(xué)基礎(chǔ)[J];解剖科學(xué)進(jìn)展;1998年01期

9 吉秀亮;張勤麗;牛僑;郭衛(wèi)力;楊焱;;鋁電解工人神經(jīng)行為功能及mGluR1表達(dá)的改變[J];環(huán)境與職業(yè)醫(yī)學(xué);2009年02期

10 楊焱;張勤麗;郭衛(wèi)力;吉秀亮;潘寶龍;牛僑;;氯化鋁致原代培養(yǎng)小鼠神經(jīng)細(xì)胞毒性作用及對mGluR3表達(dá)的影響[J];環(huán)境與職業(yè)醫(yī)學(xué);2010年01期

相關(guān)博士學(xué)位論文 前1條

1 梁瑞峰;亞慢性鋁暴露影響Aβ生成在鋁致神經(jīng)行為損傷中的作用[D];山西醫(yī)科大學(xué);2012年

，

本文編號：1781349