發(fā)布時間：2018-03-13 17:34

  本文選題：鉛　切入點：學習記憶損傷　出處：《合肥工業(yè)大學》2017年碩士論文　論文類型：學位論文

【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損傷發(fā)育期兒童學習記憶能力,并且其損傷機制涉及方方面面,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習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)育期大鼠學習記憶能力過程中的中心調控作用;2.探究慢性鉛暴露損傷發(fā)育期大鼠學習記憶能力過程中H3K27me3發(fā)揮的作用;3.闡明慢性鉛暴露降低海馬區(qū)神經元中H3K27me3水平的機制;4.初步探究鉛暴露通過H3K27me3影響Wnt信號通路的機制。方法1.以PC12為神經元模式細胞,研究EZH2對細胞突起生長的影響;2.通過染色質免疫共沉淀實驗研究EZH2在鉛的神經毒性過程中發(fā)揮的作用;3.通過免疫共沉淀等實驗探究慢性鉛暴露是否通過EZH2影響神經元內H3K27me3水平;4.通過高爾基染色實驗和行為學實驗驗證慢性鉛暴露通過H3K27me3損傷發(fā)育期大鼠學習記憶能力;5.通過染色質免疫共沉淀和基因芯片技術初步探討H3K27me3損傷發(fā)育期大鼠學習記憶能力的機制。結果1.鉛暴露降低細胞內EZH2表達,影響NGF誘導的細胞突起的長度、數量;2.慢性鉛暴露影響EZH2與NGFR、EGR2和CaMKK2等基因的結合水平,改變EZH2對其表達調控作用;3.慢性鉛暴露降低了EZH2與PRC2復合體中其他組分的結合,進而降低海馬區(qū)神經元內H3K27me3水平;4.慢性鉛暴露會降低發(fā)育期大鼠海馬區(qū)神經元樹突棘密度,影響大鼠空間記憶能力,海馬區(qū)注射過表達EZH2慢病毒后,該損傷有一定程度的修復;4.慢性鉛暴露改變了H3K27me3對Wnt信號通路中關鍵蛋白表達的調控作用。結論1.H3K27me3對相關基因表達調控的改變是鉛暴露損傷大鼠學習記憶功能的主要原因;2.慢性鉛暴露通過抑制EZH2表達降低海馬區(qū)神經元中H3K27me3水平;3.鉛暴露后H3K27me3對眾多基因的表達調控發(fā)生改變,其對Wnt信號通路關鍵蛋白表達的影響可能是鉛損傷學習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.

【學位授予單位】：合肥工業(yè)大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R114

【參考文獻】

相關期刊論文 前4條

1 馮瑤,張云惠;大氣沉積顆粒中鉛的賦存狀態(tài)研究[J];新疆氣象;2005年03期

2 蔡佑振;環(huán)境鉛污染影響人體健康[J];安全與健康;2004年15期

3 錢華;環(huán)境鉛污染來源及其對人體健康的影響[J];環(huán)境監(jiān)測管理與技術;1998年06期

4 ;Inhibition of the Specific ~3H-DL-Glu Binding in the Hippocampus of Rat Brain by Lead[J];Biomedical and Environmental Sciences;1998年01期

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本文編號：1607413