apoe基因敲除鼠眼底amd样改变及其与mbd2相关性的初步分析word格式论文.docxVIP

缩略词英文缩略词英文缩略语中文全称ApoE BSA BM ECMBD2ApolipoproteinEBovineserumalbumin Bruch’smembraneEndotheliumcellMethyl-CpGbindingdomainprotein2载脂蛋白E牛血清白蛋白玻璃膜内皮细胞甲基化结合域蛋白2RPERetinalpigmentepithelial cell视网膜色素上皮细胞PBSPhosphatebuffered saline磷酸盐缓冲液ApoE基因敲除鼠眼底AMD样改变及其与MBD2相关性的初步研究华中科技大学同济医学院附属同济医院眼科研究生：潘俊如导师：胡军副教授中文摘要【目的】探讨MBD2基因在ApoE-/-小鼠建立的年龄相关性黄斑变性（AMD）模型中的作用及影响。【方法】选择8周龄大小Mbd2-/-ApoE-/-小鼠12 只(24只眼)为实验组，ApoE-/-小鼠12 只(24 只眼)为对照组，经过4 个月西方饮食诱导，检测血清总胆固醇水平，取眼球标本行电镜检测，观察玻璃膜超微结构改变，免疫荧光检测视网膜脉络膜细胞间粘附分子-1(ICAM-1)表达。【结果】Mbd2-/-ApoE-/-小鼠与ApoE-/-小鼠总胆固醇水平无统计学差异（P0.05），电镜显示ApoE-/-小鼠眼底出现类似人AMD样改变，表现为RPE细胞基底部内折紊乱，视网膜下沉积物堆积及玻璃膜增厚现象，并且单敲组较双敲组小鼠玻璃膜厚度明显增厚（P0.05）。Mbd2-/-ApoE-/-小鼠与ApoE-/-小鼠眼球免疫荧光检测发现单敲组脉络膜ICAM-1表达较双敲组增多。【结论】MBD2基因敲除在ApoE-/-小鼠建立的老年性黄斑变性小鼠模型中可能通过减少脉络膜内皮细胞活化，改善微循环，减少脂质沉积从而减轻AMD的病变发展，对临床治疗AMD提供了新的治疗途径。关键词：MBD2老年性黄斑变性内皮细胞功能障碍ICAM-1The Effect ofMethyl-CpG Binding Domain Protein2 (MBD2) onAMD-like lesions inApoE-Deficient MouseDepartmentofOphthalmology,TongjiHospital,TongjiCollege,HuazhongUniversityofScienceandTechnologyPostgraduate:PanJunru Tutor:Porf.HuJunAbstractObjective:ToinvestigatetheroleofMBD2inApoE-deficientmouseemployedasamodelofage-relatedmaculardegeneration(AMD).Methods: Eight-week-old Mbd2-/-ApoE-/-mice (n=12, 24 eyes) and ApoE-/-mice(n=12,24eyes)werefedwithWestern-typedietfor4months.Thenthemiceweresacrificed,totalserumcholesterollevelswereanalyzedandBruch’smembranes(BM) oftheeyeswerepreparedforultrastructuralobservationbytransmissionelectronmicroscopy.Moreover,intercellularadhesionmolecule-1(ICAM-1)immunoreactivitieswereevaluatedbyfluorescencemicroscopeinsectionsoftheeyesofbothgroupsfor furtherunderstandingthefunctionmechanismofMBD2.Results:ThelevelsofthetotalserumcholesterolinApoE-/-miceshowednoobviousdifferencetothatofMbd2-/-ApoE-/-mice(P0.05).TransmissionelectronmicroscopyshowedAMD-likelesionsinApoE-/-mice:variousvacuolesaccumulatedinBruch’s membrane,notableoutercollagenouslayerdepositsanddilatedbasalinfoldingsof RPE.Morethanthat,ApoE-/-micehadamuchthickerBMthanMbd2-/-ApoE-/-m