SDF-1α在体内对骨髓间充质干细胞的保护作用及其对缺血心脏修复的影响  

Protective action of SDF-1α protects mesenchymal stem cells in vivo and its effects on the repairment for the ischemic heart

作　　者：吴原波[1] 尹琪[1] 金培峰[1] 黄伟聪[1] 旷文安[1] 孙成超[1] 

机构地区：[1]温州医学院附属第一医院心胸外科,浙江温州325000

出　　处：《温州医学院学报》2011年第2期136-140,145,共6页Journal of Wenzhou Medical College

基　　金：温州市科技局对外合作项目(h20090019)

摘　　要：目的:研究基质细胞衍生因子1α(SDF-1α)在体内对移植干细胞的保护作用及能否提高干细胞移植对缺血心脏的疗效。方法:将用2μg/mL SDF-1α预处理过的干细胞与未处理组干细胞置于低氧无血清条件下6 h,用ELISA法检测VEGF的分泌。建立大鼠心梗模型,在梗死心肌与正常心肌边缘区注射50μL不含干细胞的IMDM(对照组,n=18)或含有3×106干细胞的IMDM(MSCs组,n=18)或含有3×106干细胞与2μg hSDF-1α的IMDM(SDF-1α+MSCs组,n=18)。4 d后,用Western blot检测生存因子Bcl-2、磷酸化Akt4的表达,ELISA法检测VEGF及SDF-1α的表达量。4周后,接受心超检测、免疫组化染色。结果:SDF-1α蛋白能促进体内和体外环境下VEGF的分泌。Western blot证实经SDF-1α处理后,促生存因子Akt和Bcl-2表达增加。心梗后4周,相比单纯MSCs组而言,SDF-1α+MCSs组能更多地促进新生血管的生成。但是在心功能方面,SDF-1α+MCSs组和MSCs组没有明显差别。结论:SDF-1α能促进骨髓间充质干细胞的旁分泌作用,提高生存因子的表达,促进毛细血管新生,但未能加强干细胞移植对心功能的改善作用。Objective： To observe the effect of the stromal cell-derived factor-1α protein on the protection of MSCs and repairment of the infacted heart in vivo.Methods： Cultured MSCs pretreated with SDF-1α protein（2μg/mL）and control MSCs were subjected to hypoxia/serum deprivation（hypoxia/SD）for 6 hours,then the expression of VEGF was detected by ELISA.Myo-cardial infarction（MI）was induced in Sprague-Dawley rats by permanent ligation of the left anterior descending（LAD） artery.Then the animals were grouped to receive multiple intramyocardial injections of 50μl basal IMDM without MSCs（group-control,n=18）or containing 3×106 MSCs（group-MSCs,n=18）or 2μg hSDF-1α plus 3×106 MSCs（group-SDF-1α＋MSCs,n=18）.Four days later,the animals were sacrificed to receive western blot to detect the expression of Bcl-2 and P-Akt,and to observe the secretion of VEGF and SDF-1α with ELISA.After 4 weeks,echocardiography studies and immunohistochemistry were received.Results： SDF-1α protein could promote the expression of VEGF in vitro and in vivo as well.Western blot showed that survival signals,such as Akt/Bcl-2 were activated by in vivo SDF-1α treatment 4 days after AMI.At 4 weeks post AMI,more angiogenesis was observed in SDF-1α treatment group than that in MSCs group.But no significance was found between SDF-1α treatment group and MSCs group on LV function.Conclusion： Our data suggest that SDF-1α can enhance the paracrine of MSCs,expression of survival signals and angiogenesis,but fail to augment MSCs-mediated improvement of heart function.

关 键 词：基质细胞衍生因子1Α 骨髓间充质干细胞 心肌梗死 移植 毛细血管新生 

分 类 号：R654.2[医药卫生—外科学]