脂肪干细胞可协同麦考酚吗乙酯减轻大鼠心脏移植急性排斥反应  

Synergistic effect of adipose-derived mesenchymal stem cells and mycophenolate mofetil on alleviating the acute rejection of cardiac transplantation in rats

作　　者：胡志斌[1] 严志焜[1] 王惠菊[1] 毛文帅[1] 葛根贤[1] 

机构地区：[1]浙江省人民医院杭州医学院附属人民医院心胸外科,杭州310014

出　　处：《新医学》2017年第9期629-633,共5页Journal of New Medicine

基　　金：浙江省医药卫生科技项目(2015KYB028)

摘　　要：目的评估供体同系脂肪源性干细胞(ADSC)协同麦考酚吗乙酯(MMF)减轻大鼠心脏移植急性排斥反应的作用。方法以Wistar、SD大鼠各48只为供受体建立心脏颈部异位移植模型,实验分为4组,每组12只。未处理组,术毕仅补充生理盐水;MMF组,术后给予口饲MMF 20 mg/(kg·d),共7 d;ADSC组,术毕静脉输注ADSC(10×10~6/只);MMF+ADSC组,术毕输注ADSC(10×10~6/只),并给予口饲MMF 20 mg/(kg·d),共7 d。比较各组移植心脏存活时间和组织病理学改变,检测术后第7日血清中IL-2和IL-10的表达情况。结果未处理组移植心脏存活时间为(6.17±1.17)d,MMF组为(14.00±1.19)d,ADSC组为(21.00±4.90)d,MMF+ADSC组为(29.83±0.41)d。与未处理组比较,MMF组、ADSC组、MMF+ADSC组移植心脏存活时间均得到延长(P均<0.0083)。病理学检查发现MMF+ADSC组淋巴细胞浸润、心肌间质水肿、心肌细胞损害程度最轻。与未处理组比较,各处理组IL-2均降低、而IL-10升高(P均<0.0083);各处理组间比较,IL-2在MMF组和MMF+ADSC组较ADSC组降低(P均<0.0083);各处理组间IL-10比较差异无统计学意义(P>0.05)。在MMF+ADSC组IL-2/IL-10比值下降最为明显。结论供体同系脂肪源性干细胞具有协同霉酚酸酯减轻大鼠心脏移植急性排斥反应的作用,延长移植心脏的存活。Objective To investigate the synergistic effect of adipose-derived mesenchymal stem cells （ADSC） and mycophenolate mofetil （MMF） upon mitigating the acute rejection of cardiac transplantation in rat models.Methods Fourty-eight Wistar rats as the donors and 48 SD rats as the recipients were utilized to establish rat models with heterotopic heart transplantation in the neck.All rats were randomly divided into four groups（n=12）.In the untreated group, normal saline alone was administered after surgery.In the MMF group, MMF was orally administered at a dose of 20 mg/kg daily for 7 d.In the ADSC group, 10＆#215;106 of ADSCs were injected for each rat via intravenous route.In the MMF＋ADSC group, 10＆#215;106 of ADSC combined with MMF at a dose of 20 mg/kg daily was given for 7 d.The graft survival and histopathological changes were compared among different groups.The expression levels of serum IL-2 and IL-10 were quantitatively measured at postoperative 7 d.Results Compared with the untreated group [（6.17＆#177;1.17）d], the mean graft survival in the MMF[（14.00＆#177;1.19）d], ADSC[（21.00＆#177;4.90）d] and MMF＋ADSC group[（29.83＆#177;0.41）d] were significantly prolonged（all P＆lt;0.0083）.Pathological examination revealed that that the degree of lymphocyte infiltration, myocardial interstitial edema and myocardial cell damage was the slightest in the MMF＋ADSC group.Compared with the untreated group, the expression of serum IL-2 was dramatically down-regulated, whereas that of serum IL-10 was significantly up-regulated in the other groups （all P＆lt;0.0083）.The expression levels of IL-2 in the MMF and MMF＋ADSC groups were significantly down-regulated than that in the ADSC group （both P＆lt;0.0083）.The expression of IL-10 did not significantly differ among these three groups （all P＆gt;0.05）.The most significant decrease in the IL-2/IL-10 ratio was noted in the MMF＋ADSC group.Conclusions Donor ADSC and MMF exert a synergistic effect upon relieving the acute re

关 键 词：脂肪源性干细胞 心脏移植 急性排斥反应 免疫抑制 

分 类 号：R654.2[医药卫生—外科学]