脂肪源性干细胞输注剂量对抑制大鼠心脏移植急性排斥反应的影响
投稿时间:2017-02-28  修订日期:2017-03-24  点此下载全文
引用本文:胡志斌,严志焜,王惠菊,毛文帅,葛根贤.脂肪源性干细胞输注剂量对抑制大鼠心脏移植急性排斥反应的影响[J].医学研究杂志,2017,46(12):50-53,89
DOI: 10.11969/j.issn.1673-548X.2017.12.013
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作者单位E-mail
胡志斌 310014 杭州, 浙江省人民医院心胸外科 hulinet169@163.com 
严志焜 310014 杭州, 浙江省人民医院心胸外科  
王惠菊 310014 杭州, 浙江省人民医院心胸外科  
毛文帅 310014 杭州, 浙江省人民医院心胸外科  
葛根贤 310014 杭州, 浙江省人民医院心胸外科  
基金项目:浙江省医药卫生科技项目(2015KYB028)
中文摘要:目的 观察供体同系脂肪源性干细胞(ADSCs)对大鼠心脏移植急性排斥反应的抑制作用,并探讨其输注剂量对其抑制作用的影响。方法 以Wistar、SD大鼠为供受体建立心脏颈部异位移植模型,术毕静脉输注不同剂量ADSCs。实验分组:①对照组,注射等体积3ml 0.9% NaCl;②输注ADSCs,0.1×106/只组;③输注ADSCs,1×106/只组;④输注ADSCs,10×106/只组;每组12只。比较各组移植心脏存活时间和组织病理学改变,及检测血清中IL-2和IL-10的表达。结果 对照组移植心脏平均存活6.2±1.2天,输注不同剂量ADSCs (0.1×106/只,1×106/只,10×106/只)各组移植心脏平均存活分别为10.0±1.3天,13.3±2.2天,21.0±4.9天。与对照组比较,输注各组移植心脏存活均得到显著延长(P<0.05)。病理学检查发现ADSCs输注组淋巴细胞浸润、心肌间质水肿、心肌细胞损害均较对照组减轻。与对照组比较,ADSCs输注组大鼠血清中IL-2浓度随着ADSCs浓度增加而逐步降低,且ADSCs 10×106/只组差异有统计学意义(P=0.021);IL-10浓度呈剂量相关性逐渐增高,各组间比较差异有统计学意义(P<0.05)。结论 静脉输注供体同系ADSCs,可以延长大鼠颈部移植心脏的存活时间,减轻急性排斥反应的程度,并具有一定剂量依懒性;其中以10×106/只剂量的抗排斥作用最显著。
中文关键词:脂肪源性干细胞  心脏移植  急性排斥反应  免疫抑制
 
Effect of Adipose-derived Mesenchymal Stem Cells by Different Doses on the Acute Rejection in Rat Cardiac Transplantation Models
Abstract:Objective To investigate effect of adipose-derived mesenchymal stem cells on the acute rejection in rat cardiac transplantation models and study the possible enhancement role by infusion more ADSCs.Methods Forty-eight SD rats bearing transplanted heart from Wistar rats were divided randomly into 4 groups (n=12):①Control group:3ml 0.9%NaCl solution was injected through vena after heart transplantation. ②Treatment groups(Ⅰ,Ⅱ,Ⅲ):0.1×106 ADSCs or 1×106 ADSCs or 10×106 ADSCs in 3ml 0.9%NaCl solution was injected respectively through vena after heart transplantation. One week after transplantation, 6 rats randomly from each group were anaesthetized to get blood and allografts. Grafts pathology was studied. Serum levels of IL-2 and IL-10 was detected by method of ELISA. The rest 6 rats in each group was observed survival time of grafts.Results The survival time of grafts:Control group was 6.2±1.2days, Treatment groupⅠ,Ⅱ,Ⅲ respectively was 10.0±1.3days, 13.3±2.2days, 21.0±4.9days(P<0.05).Pathology grade:It showed that lymphocyte infiltration, myocardial interstitial edema and myocardial cell damage were decreased in treatment groups compared with the control group.Concentrations of serum IL-2:It decreased gradually with the increase of ADSCs concentration. And compared with the control group, there was significant difference in ADSCs 10×106 treatment group(P<0.05). IL-10:It increased gradually with the increase of ADSCs concentration. And there was significant difference each other(P<0.05).Conclusion Intravenous infusion of donor ADSCs could prolong the survival time of the rat cardiac allograft and inhibit acute rejection with a dose-dependent lazy. And the dose of 10×106/showed that inhibition was the best.
keywords:Adipose-derived mesenchymal stem cells  Heart transplantation  Acute rejection  Immunosuppressive
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