本文選題：鉛　切入點(diǎn)：學(xué)習(xí)記憶損傷　出處：《合肥工業(yè)大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：鉛是一種廣泛存在的環(huán)境污染物,許多研究表明慢性鉛暴露會(huì)損傷發(fā)育期兒童學(xué)習(xí)記憶能力,并且其損傷機(jī)制涉及方方面面,表觀遺傳作為聯(lián)系環(huán)境因素和遺傳因素的橋梁在鉛暴露損傷學(xué)習(xí)記憶能力的過程中發(fā)揮什么樣的作用尚不清楚。目的1.闡明EZH2在鉛暴露損傷發(fā)育期大鼠學(xué)習(xí)記憶能力過程中的中心調(diào)控作用;2.探究慢性鉛暴露損傷發(fā)育期大鼠學(xué)習(xí)記憶能力過程中H3K27me3發(fā)揮的作用;3.闡明慢性鉛暴露降低海馬區(qū)神經(jīng)元中H3K27me3水平的機(jī)制;4.初步探究鉛暴露通過H3K27me3影響Wnt信號(hào)通路的機(jī)制。方法1.以PC12為神經(jīng)元模式細(xì)胞,研究EZH2對(duì)細(xì)胞突起生長(zhǎng)的影響;2.通過染色質(zhì)免疫共沉淀實(shí)驗(yàn)研究EZH2在鉛的神經(jīng)毒性過程中發(fā)揮的作用;3.通過免疫共沉淀等實(shí)驗(yàn)探究慢性鉛暴露是否通過EZH2影響神經(jīng)元內(nèi)H3K27me3水平;4.通過高爾基染色實(shí)驗(yàn)和行為學(xué)實(shí)驗(yàn)驗(yàn)證慢性鉛暴露通過H3K27me3損傷發(fā)育期大鼠學(xué)習(xí)記憶能力;5.通過染色質(zhì)免疫共沉淀和基因芯片技術(shù)初步探討H3K27me3損傷發(fā)育期大鼠學(xué)習(xí)記憶能力的機(jī)制。結(jié)果1.鉛暴露降低細(xì)胞內(nèi)EZH2表達(dá),影響NGF誘導(dǎo)的細(xì)胞突起的長(zhǎng)度、數(shù)量;2.慢性鉛暴露影響EZH2與NGFR、EGR2和CaMKK2等基因的結(jié)合水平,改變EZH2對(duì)其表達(dá)調(diào)控作用;3.慢性鉛暴露降低了EZH2與PRC2復(fù)合體中其他組分的結(jié)合,進(jìn)而降低海馬區(qū)神經(jīng)元內(nèi)H3K27me3水平;4.慢性鉛暴露會(huì)降低發(fā)育期大鼠海馬區(qū)神經(jīng)元樹突棘密度,影響大鼠空間記憶能力,海馬區(qū)注射過表達(dá)EZH2慢病毒后,該損傷有一定程度的修復(fù);4.慢性鉛暴露改變了H3K27me3對(duì)Wnt信號(hào)通路中關(guān)鍵蛋白表達(dá)的調(diào)控作用。結(jié)論1.H3K27me3對(duì)相關(guān)基因表達(dá)調(diào)控的改變是鉛暴露損傷大鼠學(xué)習(xí)記憶功能的主要原因;2.慢性鉛暴露通過抑制EZH2表達(dá)降低海馬區(qū)神經(jīng)元中H3K27me3水平;3.鉛暴露后H3K27me3對(duì)眾多基因的表達(dá)調(diào)控發(fā)生改變,其對(duì)Wnt信號(hào)通路關(guān)鍵蛋白表達(dá)的影響可能是鉛損傷學(xué)習(xí)記憶功能的重要原因。
[Abstract]:Lead is a widespread environmental pollutant, many studies show that chronic lead exposure can damage the development of children's ability of learning and memory, and the mechanism of injury involving all aspects of epigenetics as a bridge between genetic and environmental factors in the process of learning and memory ability of lead exposure injury plays what role is not clear 1.. To clarify the EZH2 exposure center role during the development of injury of learning and memory abilities of rats in the lead; 2. to explore the chronic lead exposure rats during development process of H3K27me3 damage the ability of learning and memory in the role of the 3. states; chronic lead exposure mechanism to reduce H3K27me3 levels of hippocampal neurons in 4. lead exposure through the preliminary inquiry; the mechanism of H3K27me3 effect of Wnt pathway. Methods 1. PC12 patterns of neuronal cells, the effects of EZH2 on the growth of cell processes; 2. through chromatinimmune Co Experimental study on precipitation of EZH2 play in the lead role in the process of neurotoxicity; 3. by CO immunoprecipitation experiments to explore whether chronic lead exposure through the level of H3K27me3 in neurons of EZH2; 4. by Golgi staining experiments and behavioral experiments by H3K27me3 damage during the development of learning and memory abilities of rats with chronic lead exposure; 5. through chromatinimmune co precipitation and microarray technology to investigate mechanisms of learning and memory ability of rats during H3K27me3 damage development. Results of the 1. lead exposure reduced the expression of EZH2 in cells, the length of the influence of the number of cell processes induced by NGF; 2. chronic lead exposure effects of EZH2 and NGFR, combined with the level of EGR2 and CaMKK2 genes, the expression change of EZH2 gene regulation on the 3.; chronic lead exposure reduced with other components of the EZH2 and PRC2 complex, and then reduce the level of H3K27me3 in hippocampus neurons; 4. chronic lead exposure Will reduce the development period of hippocampal neuronal dendritic spines, affecting the spatial memory ability of rats hippocampus injected lentiviral EZH2 expression after repair to a certain extent of the damage; 4. chronic lead exposure alters the regulation role of H3K27me3 on the expression of key proteins in Wnt signaling pathway. Conclusion 1.H3K27me3 regulates the expression of related genes the main reason is the change of lead exposure damage the function of learning and memory in rats; 2. chronic lead exposure through inhibiting the expression of EZH2 decreased the level of H3K27me3 in hippocampal neurons; change regulation of H3K27me3 on expression of many genes occurred in 3. after lead exposure, the effect of Wnt signaling pathway key protein expression may be an important cause of lead damage the function of learning and memory.

【學(xué)位授予單位】：合肥工業(yè)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R114

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