外源性VEGF165调节骨骼肌成肌细胞移植诱导的Th17/Treg失衡  

Exogenous VEGF165 regulates skeletal myoblasts transplantation induced Th17/Treg imbalance

作　　者：柳瑞军[1] 过常发[2] 陈昶[1] 姜格宁[1] 

机构地区：[1]同济大学附属上海市肺科医院胸外科,200433 [2]复旦大学附属中山医院心外科

出　　处：《中华胸心血管外科杂志》2014年第4期242-246,共5页Chinese Journal of Thoracic and Cardiovascular Surgery

摘　　要：目的 探讨骨骼肌成肌细胞移植治疗急性心肌梗死（AMI）时,是否存在幼稚Th淋巴细胞的Th17细胞（Th17）和调节性T细胞（Tregs）之间的Th 17/Treg失衡,血管内皮生长因子165（VEGF165）是否可缓解这种失衡.方法 C57BL/6雄性小鼠60只,3～4周龄,体质量0.016 ～0.020 kg.数字表法随机分为3组：AMI组、AMI-S组和AMI-Ⅴ组,每组20只.AMI组为对照组,AMI-S组为异体骨骼肌成肌细胞移植组,AMI-Ⅴ组为心肌梗死VEGF165治疗组.分别于异体骨骼肌成肌细胞移植（SMT）1、2、4和7天后,用流式细胞仪分析3组小鼠的Th17和Treg细胞比率.蛋白芯片和实时聚合酶链反应分别检测有关促炎细胞因子、调节性细胞因子、关键转录因子、ROR-γt mRNA以及Foxp3 mRNA的表达.结果 与AMI组相比较,1、2、4、7天后,AMI-S组的调节细胞百分比、有关细胞因子浓度和转录因子Foxp3mRNA低,AMI-Ⅴ组高;AMI-S组的Th17细胞百分比、有关细胞因子浓度和ROR-γt mRNA高,AMI-Ⅴ组低;AMI-S组中Th 17/Treg细胞比率显著增加,而AMI-Ⅴ组明显减少.结论 异体SMT后,炎性和免疫反应形成和发展过程中存在Th17/Treg失衡.转染VEGF165可减缓TH 17/Treg失衡.Objective To investigate whether Th17/Treg imbalance existed,and whether VEGF165 attenuated the imbalance in allogeneic skeletal myoblasts transplantation（allo-SMT） for acute myocardial infarction （AMI）.Methods There were 60 C57BL/6 male mice,3 to 4 weeks old,weighting 0.016-0.020 kg.On the day 1,2,4,and 7 after allo-SMT,the percentages of Th17 and Treg cells,and the ratios of Th17/Treg cells were analyzed by FCM in AMI group,AMI-S group（alloSMT） and AMI-Ⅴ group（with VEGF165 treatment）.Subsequently,related proinflammatory and regulatory cytokines and key transcription factors ROR-γt mRNA and Foxp3 mRNA expression were examined by Bio-plex and RT-PCR respectively.Results On the day 1,2,4,and 7 after allo-SMT,the percentage of Treg,related cytokines concentrations and transcript factor Foxp3 mRNA in AMI-S group were lower than those in AMI group,while the AMI-Ⅴ group were higher than those in AMI groups.However,the percentage of Th17 cells,related cytokines concentrations,and ROR-γt mRNA in AMI-S group were higher than those in AMI group; but the AMI-Ⅴ group were lower than those in AMI group.Apparently,compared with AMI group,the ratios of Th17/Treg significantly ascended in AMI-S group and decended in AMI-Ⅴ group.Conclusion Th17/Treg imbalance participated in the formation and development of inflammation and immune response after allo-SMT.However,transfected VEGF165 could relieve the severity of Th17/Treg imbalance.

关 键 词：成肌细胞 骨骼肌 细胞移植 血管内皮生长因子类 

分 类 号：R542.22[医药卫生—心血管疾病]