pgc-1α去乙酰化在mpp+诱导sh-sy5y细胞氧化损伤的影响

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1、分类号：R741.02学校代码：10392学科专业代码：100204学号：200903118福建医科大学硕士学位论文+PGC-1α去乙酰化在MPP诱导SH-SY5Y细胞氧化损伤的影响+EffectsofPGC-1αdeacetylationonMPP-inducedoxidativedamageinSH-SY5Ycells学位类型：医学硕士所在学院：协和临床医学院申请人：范飞学科、专业：神经病学导师：叶钦勇副教授研究起止日期：2012年1月至2013年3月答辩日期：2013年5月31日二○一三年六月目录英文缩略词表······················

2、·································1中文摘要···························································2英文摘要··························································4引言·····························································61材料与方法···················································

3、82结果·······················································183讨论·······················································224结论·······················································25参考文献··························································26综述···································

4、·························28英文缩略语表(Abbreviation)缩写英文全称中文全称SH-SY5YHumanneuroblastomacell人神经母细胞瘤细胞SIRT1Silenceinformationregulator1沉默信息调节因子2相关酶类1PGC-1αPeroxisomeproliferatoractivatedreceptor过氧化物酶体激活物受体辅激活因gammacoactivator-1α子1αSRT1720N-(2-(3-(1-Piperazinylmethyl)N-[2-[3-(1-哌嗪甲基)咪唑并[2,

5、1-b]imidazo[2,1-b]thiazol-6-yl)phenyl)-噻唑-6-基]苯基]-2-喹喔啉甲酰胺盐2-quinolinecarboxamide酸盐EX5276-chloro-2,3,4,9-tetrahydro-1h-carbazole6-氯-2,3,4,9-四氢-1H-咔唑-1-甲酰1-carboxamide胺+MPP1-methyl-4-phenylpyridiniumion1-甲基-4-苯基-1,2,3,6-四氢吡啶离子THTyrosinehydroxylase酪氨酸羟化酶PDParkinson’sDisease帕金森病ROSrea

6、ctiveoxygenspecies活性氧集团PMSFPhenylmethanesulfonylfluoride苯甲基磺酰氟Tris2-amino-2-hydroxymethyl-1,3-propanediol三羟甲基氨基甲烷1+PGC-1α去乙酰化对MPP诱导SH-SY5Y细胞氧化损伤的影响中文摘要【背景】过氧化物酶增殖物激活受体γ（PPARγ）辅激活因子1α（PGC-1α）可强有力调控氧化和抗氧化过程，在线粒体生物学过程和氧化应激中具有突出的作用，其广泛参与各种新陈代谢通路的调节，如能量代谢、线粒体生物合成、糖脂代谢+等。PGC-1α转录活性受内源性去乙

7、酰化酶SIRT1调节。SIRT1在MPP诱导的SH-SY5Y细胞氧化应激损伤中作用机制未见报道，在氧化应激时是否起到上调和维持PGC-1α的积极作用也未见报道。【目的】1、探讨SIRT1对PGC-1α去乙酰化的影响。+2、明确去乙酰化对PGC-1α在MPP诱导SH-SY5Y细胞内作用的影响，并寻找其中的重要分子机制。【方法】1、细胞免疫组化检测TH。+2、MTT法检测细胞活力，观察不同浓度MPP、SRT1720、EX527干预SH-SY5Y细胞24h后的细胞活力变化。3、使用流式细胞仪技术检测SH-SY5Y细胞胞内ROS水平。4、Western-Blot免疫

8、印迹法检测SH-SY5Y细胞内SIRT1、PGC-1