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ID:32230169
大小:1.66 MB
页数:70页
时间:2019-02-01
《间充质干细胞对大鼠同种异体心脏移植的影响》由会员上传分享,免费在线阅读,更多相关内容在学术论文-天天文库。
1、间充质干细胞对大鼠同种异体心脏移植的影响博士研究生导师万连壮廖崇先教授中文摘要间充质干细胞是来源于发育早期中胚层的一类多能干细胞。近来对间充质干细胞免疫调控功能的研究,提示其在诱导器官移植免疫耐受中的应用前景。本研究从大鼠骨髓中分离出间充质干细胞,建立大鼠同种异位心脏移植模型,旨在研究骨髓间充质干细胞在心脏移植中诱导免疫耐受,减少免疫排斥的作用,并探讨其可能机制。本研究第一部分采用密度梯度离心及贴壁传代培养法,得到大鼠骨髓问充质干细胞;第二部分以雄性Sprague—Dawley(sD)大鼠为受体,Wist
2、ar大鼠为供体,建立大鼠同种异位心脏移植模型,移植成功率达95%以上;第三部分采用3H-胸腺嘧啶核苷掺入法,检测大鼠骨髓间充质干细胞对体外混合淋巴细胞培养的影响。结果显示骨髓来源间充质干细胞不引起大鼠、淋巴细胞增殖反应,但对大鼠混合淋巴细胞培养有显著的抑制作用;第四部分探讨问充质干细胞对大鼠同种异体心脏移植的影响。异位心脏移植后受体鼠分成4组。1、空白对照组经尾静脉注射PBS;2、经尾静脉注射供体大鼠骨髓间充质干细胞;3、受体大鼠移植前1天至移植后7天,每天给予骁悉;4、受体大鼠除了接受与组3相同处理外,
3、心脏移植后经尾静脉注射供体大鼠骨髓间充质干细胞。结果显示,移植心脏的存活时间为组1:7.5±0.5天;组2:14.8±2.1天;组3:23.4±I.3天;组4:36.6±4.2天。统计学分析显示,移植心脏存活时间组2比组1明显延长(D4、O.05)。血清IL.4水平,组2、3和4均高于组l(p<0.05),组4高于组l和组2(P<0.05),但与组3相比差异不显著(pO.2)。本研究结果表明,大鼠同种异位心脏移植后静脉注射骨髓问充质干细胞可减轻心脏移植排斥反应,其机制可能与骨髓间充质干细胞抑制淋巴细胞增殖,调节细胞因子的分泌有关。【关键词】间充质干细胞大鼠骨髓心脏移植淋巴细胞免疫2Theeffectofmesenehymalstemcellsonallograflofratheartpostgraduate:LianzhuangWanSu5、pervisor:ChongxianLiaoMesenchymalstemcells(MSCs)arenmltipotentialstemcellsderivedfrommesodermofearlyphaseembryo.RecentstudiesshowedthatMSCspossessedimmunomodulatorypotential.Soitmaybeusedtoinduceimmuno—toleranceinorgantransplantation.Inthestudy,weisolated6、MSCsfromratbonemaaTowandestablishedamodelofheterotopicrathearttransplantationtoresearchtheeffectoftoleranceinductionwithMSCsonrathearttransplantationandtoexploretheunderlyingmechanism.InpartIoftheresearch,wesuccessfullyisolatedMSCsfromratbonemarrowbyingre7、dientcentrifugalization.Thecellswerepurifiedbyadheringspeciality.InpartII,wechoosedSprague—Dawley(SD)ratasrecepientandWistarratasdonoLtoestablishaheterotopicmodelofrathearttranspaIntationwithmorethan95percentofthetransplantationsuccessful.InpartIII,weexpl8、oredtheeffectofMSCsonmixedlymphocytereaction(MLR)invitroby3H-TDRincorporatingmethod.TheresultsshowedthatMSCswouldnotelicitaprolifemtiveresponseofratlymphocyte,buthadsignificantsuppressiveeffectonalloreactivityofratl
4、O.05)。血清IL.4水平,组2、3和4均高于组l(p<0.05),组4高于组l和组2(P<0.05),但与组3相比差异不显著(pO.2)。本研究结果表明,大鼠同种异位心脏移植后静脉注射骨髓问充质干细胞可减轻心脏移植排斥反应,其机制可能与骨髓间充质干细胞抑制淋巴细胞增殖,调节细胞因子的分泌有关。【关键词】间充质干细胞大鼠骨髓心脏移植淋巴细胞免疫2Theeffectofmesenehymalstemcellsonallograflofratheartpostgraduate:LianzhuangWanSu
5、pervisor:ChongxianLiaoMesenchymalstemcells(MSCs)arenmltipotentialstemcellsderivedfrommesodermofearlyphaseembryo.RecentstudiesshowedthatMSCspossessedimmunomodulatorypotential.Soitmaybeusedtoinduceimmuno—toleranceinorgantransplantation.Inthestudy,weisolated
6、MSCsfromratbonemaaTowandestablishedamodelofheterotopicrathearttransplantationtoresearchtheeffectoftoleranceinductionwithMSCsonrathearttransplantationandtoexploretheunderlyingmechanism.InpartIoftheresearch,wesuccessfullyisolatedMSCsfromratbonemarrowbyingre
7、dientcentrifugalization.Thecellswerepurifiedbyadheringspeciality.InpartII,wechoosedSprague—Dawley(SD)ratasrecepientandWistarratasdonoLtoestablishaheterotopicmodelofrathearttranspaIntationwithmorethan95percentofthetransplantationsuccessful.InpartIII,weexpl
8、oredtheeffectofMSCsonmixedlymphocytereaction(MLR)invitroby3H-TDRincorporatingmethod.TheresultsshowedthatMSCswouldnotelicitaprolifemtiveresponseofratlymphocyte,buthadsignificantsuppressiveeffectonalloreactivityofratl
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