[文章编号]1000-4718(200910-1936-05[收稿日期]2009-03-30[修回日期]2009-08-21Tel:020-********;E-mail:docliuam@yahoo.com.cn转肝细胞生长因子的脐带间质干细胞移植促进大鼠脑出血后髓鞘再生刘安民1,罗铭2,蔡望青1,李方成1,李国3,潘伟生3(中山大学附属第二医院1神经外科,2肿瘤科,广东广州510120;3香港中文大学,中国香港[摘要]目的:研究转人肝细胞生长因子(hHGF人脐带间质干细胞(hUCMSCs移植对脑出血后脱髓鞘再生和神经功能恢复的影响。方法:SD大鼠60只,随机分为3组:脑出血+hUCMSCs-HGF组、脑出血+hUCMSCs组和脑出血+PBS组,每组20只。胶原酶诱导建立脑出血模型,据不同组别于术后7d立体定向下进行侧脑室相应的移植。分别于移植前1d和移植后1、7、14、21、28、35d利用mNSS(modifiedneurologicalseverityscores评分检测大鼠神经功能情况,应用劳克坚牢蓝检测脑损伤区的神经纤维恢复情况,利用免疫组化和Westernblotting检测髓鞘碱性蛋白(MBP的表达变化。结果:脑出血模型大鼠术后3周(即移植术后2周mNSS评分检测的神经功能,hUCMSCs-HGF组和hUCMSCs组的神经功能改善较PBS组明显提高(P<0105,而且hUCMSCs-HGF组较hUC2MSCs组神经改善更加显著(P<0105。hUCMSCs-HGF组的神经纤维修复较其它组明显改善,髓鞘碱性蛋白的表达较其它组亦明显提高(P<0101。结论:转hHGF人脐带间质干细胞移植较单纯细胞移植能明显提高神经纤维髓鞘再生能力,促进脑出血后神经功能缺失的修复。[关键词]间质干细胞;肝细胞生长因子;髓鞘再生;脑出血;大鼠[中图分类号]R743.34[文献标识码]AHepatocytegrowthfactormodifiedhumanumbilicalcordmesenchymalstemcelltherapypromotesremyelinationafterintracerebralhemorrhageinratsLIUAn-min1,LUOMing2,CAIWang-qing1,LIFang-cheng1,LIGuo3,POONWai-sang3(1DepartmentofNeurosurgery,2DepartmentofOncology,TheSecondAffiliatedHospital,SunYat-senUniversity,Guang2zhou510120,China;3ChineseUniversityofHongKong,HongKong,China.E-mail:docliuam@yahoo.com.cn[ABSTRACT]AIM:Tostudytheeffectsofneurologicalimprovementandremyelinationafterintracranialhemor2rhage(ICHinratsbyanoveltherapeuticstrategywithhepatocytegrowthfactor(HGFgenetransfectedhumanumbilicalcordmesenchymalstemcells(hUCMSCsbylentiviralvector.METHODS:ICHwasinducedin60adultmaleSprague-DawleyratsbyastereotacticallyguidedinjectionofbacterialtypeIVcollagenaseintotherightinternalcapsule.Non-mod2ifiedhUCMSCs,HGF-modifiedhUCMSCswithlentiviralvectororPBSwereadministeredleftintraventricularly7dafterrightinternalcapsuleICH.Allratsunderwentmodifiedneurologicalseverityscoresfor35d.Luxolfastbluestaining,im2munohistologicalstainingandWesternblottingassessmentsformyelinbasicprotein(MBPwereapplied.RESULTS:TheICHratsreceivingHGF-modifiedhUCMSCsdemonstratedsignificantfunctionalrecovery,determinedbymodifiedneuro2logicalseverityscores,comparedtotheothergroupsfrom2weeksaftercelltherapy.AsindicatedbyLuxolfastbluestai2ning,thepercentareaofdemyelinationwasobviouslyreducedintheHGF-hUCMSCtreatmentgroupcomparedtothePBScontrolgroupandhUCMSC-onlytreatmentgroupat5weeksafterICH.TheexpressionofMBPdetectedbyimmunohisto2logicalstainingandWesternblottingwassignificantlyhigherinHGF-hUCMSCstreatedbrainthanthatinothergroups(P<0101.CONCLUSION:OurdatasuggestthattheHGFgene-modifiedhUCMSCscontributetotheremarkablefunc2tionalrecoveryafterICHcomparedtohUCMSCstransplantationalone.Thetreatmentpromotesnervefiberremyelinationby・6391・中国病理生理杂志ChineseJournalofPathophysiology2009,25(10:1936-1940up-regulatingtheMBPafterICHinrats.[KEYWORDS]Mesenchymalstemcells;Hepatocytegrowthfactor;Remyelination;Brainhemorrhage;Rats自发性脑出血(intracranialhemorrhage,ICH是一种临床常见病,其发病率、死亡率很高,即使生存...