cski基因对小梁通道房水外流阻力的调控及机制分析word格式论文.docx

13.02±0.48mmHg和13.05±0.52mmHg，差别无统计学意义(P0.05，n=12)。病毒注射后第11天，治疗组眼压开始下降，与对照组相比，差别有统计学意义(P0.05)；第13天开始，治疗组眼压与基线眼压及对照组眼压相比，差别均有统计学意义(P0.05)；之后治疗组眼压持续下降，稳定在一个相对低水平，直至第21天处死。纳入的12 只大鼠未见明显的角膜、前房炎症反应及其它眼部异常。4、免疫细胞化学结果显示：大鼠前房注射病毒后4周，实验组小梁网细胞外基质(extracellularmatrix,ECM)和细胞肌动蛋白骨架蛋白均表达减弱。结论：1、成功构建pCDF1-MCS2-EF1-copGFP-c-Ski慢病毒表达载体，在293TN细胞中包装得到具有感染能力的病毒颗粒。2、病毒转导小梁细胞，在小梁细胞中表达c-Ski，并经免疫细胞化学和Western-blot证实，c-Ski基因可引起人小梁细胞肌动蛋白骨架的降解及细胞连接蛋白β-catenin表达减少。3、慢病毒介导的c-Ski在大鼠小梁网ECM蛋白的表达及肌动蛋白和相关连接蛋白的表达减弱。4、HIV-c-Ski前房内注射能降低大鼠眼压，治疗效果优于HIV-GFP组。其降眼压机制可能是通过小梁通道表达c-Ski基因抑制TGF-β/Smad信号通路，降解肌动蛋白和ECM来实现。关键词：C-Ski，基因治疗，青光眼，眼压，慢病毒。基金项目：国家自然科学基金资助项目（NOTheregulationandmechanismresearchofc-Skigeneon aqueoushumoroutflowresistanceinTrabecularchannelABSTRACTBackgroundandobjective:Primaryopen-angle glaucoma（POAG)isamajorof blindingeye diseasesthatislate-onset,progressiveandirreversible.Atpresentitspathogenesisisnotfullyclear,butgenerallythinkelevatedintraocular pressureisoneofthemainriskfactors.Therefore,Iopreductionhasbeen theprincipalmeansofglaucomatreatment.TodaymostofIOP reductiondrugsincurativeeffectisnot ideal, andhavecertainside effects.Oncesufferingfromglaucomarequiresmedicationforalong time,sothere are problemslike highcostandpoor treatmentadherenceet al.Moreover,intermsofmechanismindrugaction,inadditionto cholinergicagonist(aspilocarpine),othereffectsinmedicinedidnot focusonthemainexhaustpassageoftheaqueoushumororTrabecular channels.Therefore,therearemanyproblemsinthecurrentIOP reductiontreatment,theintroductionofgenetherapyhasaspecial significance.Thistopicintheapplicantsonthebasisofpreviouswork, theauxiliaryrepressorofTGF-beta/Smad signaling pathways c-Ski geneintoanteriorchamberofrats,exploringc-skigeneexpressionon aqueoushumoroutflowofratandtheinfluenceofintraocularpressure,possible mechanismandside effectsofgeneticallymodifiedexpression.Theresearchhasnotbeenreportedathomeandabroad.Theprojectis expectedtoclarifyinc-Skithefeasibilityofgenetherapyforglaucoma, forthemajorityofpatients