大鼠胎血间充质干细胞移植对局灶性脑缺血治疗作用的研究

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1、大鼠胎血间充质干细胞移植对局灶性脑缺血治疗作用的研究【摘要】目的：研究大鼠胎血间充质干细胞(MSCs)移植入大脑中动脉栓塞(MCAO)大鼠模型后大鼠神经功能的恢复情况。方法:线栓法建立左侧大鼠MCAO模型,随机分为3组:手术组、MSCs移植组、生理盐水组。5溴2脱氧尿核苷(BrdU)标记的MSCs移植后，采用改良神经功能损伤评分系统(mNSS)评价大鼠神经功能恢复情况；应用免疫组织化学双染技术检测MSCs的存活、迁移及其巢蛋白（Nestin）、胶质纤维酸性蛋白(GFAP)和神经元特异性烯醇化酶（N

2、SE）的表达。结果:MSCs增殖能力强，并能在体外诱导分化为成骨细胞、脂肪细胞和神经元样细胞。MSCs移植后显著提高局灶性脑缺血大鼠神经功能的恢复。移植的MSCs细胞可在大鼠脑组织中存活,并向缺血区域迁移,有不同比例MSCs细胞分别表达Nestin、GFAP、NSE。结论:大鼠胎血中含有MSCs，体外扩增纯化后可促进局灶性脑缺血大鼠神经功能的恢复,移植细胞可在大鼠脑缺血区域中存活、迁移并向星形胶质细胞或神经元分化。【关键词】胎血干细胞缺氧缺血脑移植大鼠WistarATransplantationof

3、fetalbloodderivedmesenchymalstemcellsinthetreatmentofcerebralischemiainratsJUXiuli1,HUANGZhiwei1,WEIXinbing2,HOUHuaishui3,SHIQing3,LIDong3,SUNNianzheng1(1.DepartmentofPediatrics,QiluHospitalofShandongUniversity,Jinan250012,Shandong,China;2.Depart

4、mentofParmacology,SchoolofMedicine,ShandongUniversity,Jinan250012,Shandong,China;3.CryomedicineLaboratory,QiluHospitalofShandongUniversity,Jinan250012,Shandong,China)［ABSTRACT］Objective:Toobservetheroleofpurifiedmesenchymalstemcells(MSCs)derivedfromfet

5、albloodontheneurologicalfunctioninratswithmiddlecerebralarteryocclusion(MCAO).Methods:ThirtyadultmaleWistarratswererandomlydividedintothreegroups:theoperationgroup,thetransplantationofMSCsgroupandtheinjectionofsalinegroup.Functionaloutcomemeasurementsw

6、ereperformedbasedonthemodifiedneurologicalseverityscore(mNSS)atday1,7,14,21and28afterMACO.Thesurvival,migration,expressionofNestin,glialfibriliaryacidicprotein(GFAP)andneuronspecificenolase(NSE)of5bromo2deoxyuridine（BrdU）labeledMSCsweredetectedbyi

7、mmunohistochemicaldoublestaining.Results:MSCsfromthefetalbloodhadapowerfulproliferationability.MSCssignificantlyimprovedtheneurologicalfunction(P<0.05).Theengraftedcellssurvivedandmigratedtotheischemictissues.(2.88±0.76)%，(5.24±1.06)%and(1.34±1.29)%oft

8、heMSCsrespectivelyexpressedNestin,GFAPandNSE.Conclusion:Afterproliferationandpurification,theMSCsinthefetalbloodgreatlyimprovedtheneurologicalfunctioninratswithcerebralischemia,meanwhiletheymaysurvive,migrateanddifferentiateintoastrocy