供者自然杀伤细胞减轻gvhd并提高移植成活率的实验研究.doc

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1、供者自然杀伤细胞减轻GVHD并提高移植成活率的实验研究作者：黄纯兰，刘霆，陆晓茜，孟文彤【摘要】本研究观察激活的供、受者NK细胞能否减轻骨髓移植后GVHD和增加移植成活率。以C57BL/6小鼠作为供者，将接受Gy60C0Y射线全身照射的BALB/c受鼠随机分为4组，对照1组、对照2组、实验1组和实验2组，观察每组小鼠的活存期、嵌合率、GVHD临床和病理改变。结果表明：对照1组全部活存，实验1组比对照2组活存期短，实验2组比对照2组活存期延长。实验1组GVHD临床及病理评分高于对照2组，实验2组GVHD临床及病理评分明显低于对照2组。实验1组和实验2组嵌合率均较对照2组高，实验2组

2、的嵌合率比实验1组明显增加。结论：激活的供者NK细胞能延长实验小鼠的活存期，降低GVHD严重程度，增加移植成活率；而激活的受者NK细胞却缩短实验小鼠的活存期，加重GVHD严重程度。受者NK细胞也增加移植成活率，但比供者NK细胞作用小。【关键词】骨髓移植;NK细胞;GVHD;移植成活率ExperimentalStudyofDonorNaturalKillerCellsReducingGraft-versus~hostDiseaseandEnhancingEngraftmentAbstractThepurposeofthisstudywastoinvestigatewhetherpr

3、etransplantinfusionofreactivenaturalkillercellsfromdonororrecipientcanreducegraft-versus-hostdiseaseandenhanceengraftmentinbonemarrowtransplantation.RecipientBALB/cmiceweredividedinto4groupsafterrecEivedGytotal-bodyirradiation(TBI):controlgrouplwastreatedwithnothing,controlgroup2recEIvedBMTal

4、one,experimentgrouplreceivedBMTandautoreactiveNKcelIs,experimentgroup2receivedBMTandalloreactiveNKcells.Lifespan,clinicalandpathologicchangesofGVHDandchimerismrateofeachgroupwereevaluated.Theresultsshowedthatallmiceweresurvivalincontrolgroupi.Thelifespanwasshorterinexperimentgrouplthanthatinc

5、ontrolgroup2andlongerinexperimentgroup2thanthatincontrolgroup2.GVHDwashigherinscoreofexperimentgrouplthanincontrolgroup2butlowerinexperimentgroup2thanthatincontrolgroup2.Thedonorchimerismrateinbothtwoexperimentgroupswerehigherthanthatincontrolgroup2,however,thedonorchimerismratewashigherinexp

6、erimentgroup2thanthatinexperimentgroupl.ItisconcludedthatpretransplantinfusionofalloreactivedonorNKcellscanprolonglifespan,reducethedegreeofGVHDandenhanceengraftment.ButautoreactiverecipientNKcellscanshortenlifespan,aggravatethedegreeofGVHDandalsoenhanceengraftment,whichisweakerthanthatusinga

7、lloreactivedonorNKcelIs.Keywordsbonemarrowtransplantation；naturalkillercell；GVHD；engraftment骨髓移植是目前根治恶性血液肿瘤的主要方法，但其主要致死性并发症移植物抗宿主病却制约着其应用。回顾性研究发现，在骨髓移植中受者体内天然杀伤细胞增加的同时GVHD发生率降低，移植成活率增加，复发率减少［1］。我们利用动物模型分别研究了供、受者来源的NK细胞能否减轻GVHD和增加移植成活率，探索NK细胞在