过表达HGF的骨髓间充质干细胞通过PI3K/Akt/eNOS信号通路促进了大鼠缺血皮瓣的血管新生

竺 枫, 殷 杰, 薛 建波, 李 俊杰, 张 健
宁波市第六医院

摘要

目的:探讨BMSCs过表达HGF对大鼠缺血皮瓣的治疗效果｡方法:培养BMSCs并用慢病毒载体转染HGF,检测上清中HGF｡建立SD大鼠缺血皮瓣模型,注射PBS､BMSCs､BMSC-HGF,检测HGF､p-Akt､p-eNOS表达及皮瓣血流､毛细血管密度､存活率｡结果:BMSC-HGF细胞成功表达了HGF｡BMSC-HGF组在缺血皮瓣模型中较BMSCs组具有更能增强血流､血管新生和皮瓣存活,且ELISA和WesternBlot表明HGF､p-Akt､p-eNOS表达增加｡结论:HGF过表达的BMSCs通过PI3K/Akt/eNOS通路增加血管新生和血流重建,提高皮瓣存活｡

关键词

肝细胞生长因子;骨髓间充质干细胞;缺血皮瓣;内皮型一氧化氮合酶;血管新生

参考

[1]LiRG,YuB,WangG,etal.Sequentialtherapyofvacuumsealingdrainageandfree-flaptransplantationforchildrenwithextensivesoft-tissuedefectsbelowthekneeintheextremities[J].Injury,2012,43(6):822-828.[2]XuanW,KhanM,AshrafM.ExtracellularvesiclesfromNotchactivatedcardiacmesenchymalstemcellspromotemyocyteproliferationandneovasculogenesis[J].FrontCellDevBiol,2020,8:11.[3]何波,何志军,李金鹏,等.提高间充质干细胞治疗皮瓣缺血再灌注损伤的策略[J].中国组织工程研究,2024,28(19):2097-3103.[4]NakamuraT,SakaiK,NakamuraT,etal.Hepatocytegrowthfactortwentyyearson:Muchmorethanagrowthfactor[J].JGastroenterolHepatol,2011,26Suppl1:188-202.[5]SeyedJafariSM,ShafighiM,BeltraminelliH,etal.Improvementofflapnecrosisinaratrandomskinflapmodelbyinvivoelectroporation-mediatedHGFgenetransfer[J].PlastReconstrSurg,2017,139(5):1116e-1127e.[6]HsuehYY,WangDH,HuangTC,etal.Novelskinchamberforratischemicflapstudiesinregenerativewoundrepair[J].StemCellResTher,2016,7(1):72.[7]OtrockZK,MahfouzRA,MakaremJA,etal.Understandingthebiologyofangiogenesis:reviewofthemostimportantmolecularmechanisms[J].BloodCellsMolDis,2007,39(2):212-220.[8]赵毅,闫洪伟,王玉琦,等.腺病毒介导的肝细胞生长因子/血管内皮生长因子165对大鼠超比例随意皮瓣成活的影响其机制研究[J].中国美容医学,2024,33(2):60-63.[9]RahDK,YunIS,YunCO,etal.Genetherapyusinghepatocytegrowthfactorexpressingadenovirusimprovesskinflapsurvivalinaratmodel[J].JKoreanMedSci,2014,29Suppl3(Suppl3):S228-36.[10]PillK,HofmannS,RedlH,etal.Vascularizationmediatedbymesenchymalstemcellsfrombonemarrowandadiposetissue:acomparison[J].CellRegen,2015,4:8.[11]KuppuswamyS,AnnexBH,GantaVC.Targetinganti-angiogenicVEGF165b-VEGFR1signalingpromotesnitricoxideindependenttherapeuticangiogenesisinpreclinicalperipheralarterydiseasemodels[J].Cells,2022,11(17):2676.[12]ZhangY,KhoiPN,CaiB,etal.SulforaphaneregulateseNOSactivationandNOproductionviaSrc-mediatedPI3K/AktsignalinginhumanendothelialEA.hy926Cells[J].Molecules,2022,27(17):5422.[13]OmorphosNP,GaoC,TanSS,etal.Understandingangiogenesisandtheroleofangiogenicgrowthfactorsinthevascularisationofengineeredtissues[J].MolBiolRep,2021,48(1):941-950.