预输注RelB shRNA慢病毒修饰树突细胞诱导大鼠肝移植免疫耐受  

Immune tolerance of rat liver transplantation induced by pre-infusion of RNA interference RelB short hairpin RNA lentiviral modified dendritic cells

作　　者：谢金敏[1,2] 汪艳[3] 包杰[4] 马永革[2] 邹志浩[2] 唐增杰[2] 董瑞强[5] 温浩[1] 

机构地区：[1]新疆医科大学第一附属医院临床医学博士后流动站,新疆维吾尔自治区乌鲁木齐市830012 [2]解放军第23医院,新疆维吾尔自治区乌鲁木齐市830011 [3]南方医科大学珠江医院肝胆二科,广东省广州市510280 [4]南方医科大学南方医学院检验医学科,广东省广州市510515 [5]石河子大学医学院,新疆维吾尔自治区石河子市834407

出　　处：《中国组织工程研究》2012年第53期9934-9940,共7页Chinese Journal of Tissue Engineering Research

摘　　要：背景:肝移植后的排斥反应是威胁患者和移植物长期存活的主要原因。诱导受者产生特异性免疫耐受是解决排斥反应的理想措施。目的:探讨RNAi RelB树突状细胞预输注诱导大鼠肝移植特异性免疫耐受的可能性。方法:将近交系雄性清洁级DA(RT1a)大鼠和近交系雄性SPF级Lewis(RT11)大鼠分别作为供、受体,行原位肝移植手术。术前随机配对分为4组:①对照组,受体鼠移植前不做预输注。②治疗组:受体鼠移植前7d静脉输注供体大鼠RNAi RelB树突状细胞(5×106)。③未成熟树突状细胞组:受体鼠移植前7d静脉输注供体大鼠未成熟树突状细胞(5×106)。④成熟树突状细胞组:受体鼠移植前7d静脉输注供体大鼠成熟树突状细胞(5×106)。结果与结论:与对照组、未成熟树突状细胞组以及成熟树突状细胞组相比,治疗组移植肝的平均生存时间显著延长。移植后第7天,治疗组天冬氨酸转氨酶,总胆红素水平低于对照组、成熟树突状细胞组、未成熟树突状细胞组(P<0.01),移植后第14天治疗组、未成熟树突状细胞组天冬氨酸转氨酶,总胆红素均有轻微下降,两组比较差异仍有显著性意义(P<0.01)。移植后第7天,与治疗组比较,对照组、成熟树突状细胞组、未成熟树突状细胞组γ-干扰素、白细胞介素2水平升高(P<0.01),而白细胞介素4、白细胞介素10下降(P<0.01);移植后第14天治疗组、未成熟树突状细胞组γ-干扰素、白细胞介素2水平均有下降,白细胞介素4、白细胞介素10水平均有升高,两组比较差异仍有显著性意义(P<0.01)。对照组、成熟树突状细胞组、未成熟树突状细胞组移植后第7天排斥活动指数为8.0-9.0。未成熟树突状细胞组第14天肝细胞、内皮细胞坏死及汇管区炎性细胞浸润进一步增多。治疗组移植后第7天排斥活动指数为6.0-8.0,第14天时排斥活动指数为4.0-5.0。结果提示RNAi RelB树突状细胞预输注可以减�BACKGROUND： Homograft rejection is the most important factor that limits the survival of recipients and donor organs fter liver transplantation. Induced specific immune tolerance is a most satisfactory method to release rejection after transplantation. OBJECTIVE： To explore the possibility of the specific immune tolerance induced by RNA interference RelB dendritic cells pre-infusion after liver transplantation in rats. METHODS： A stable rat model of acute rejection was established by allograft liver transplantation from DA （RT1a） rats to Lewis （RT11） rats. Before transplantation, the donor and recipient rats were paired and randomly divided into four groups： （1）Control group： the recipient rats were not injected before liver transplantation. （2）RNA interference RelB treatment group： the recipient rats were pre-injected with RNA interference RelB dendritic cells from donor （5×10 6 ） via veins at the 7 days before transplantation. （3）Immature dendritic cells group： the recipient rats were pre-injected with immature dendritic cells （5×10 6 ） from donor via veins at the 7 days before transplantation. （4）Mature dendritic cells group： the recipient rats were pre-injected with mature dendritic cells （5×10 6 ） from donor via veins at the 7 days before transplantation. RESULTS AND CONCLUSION： Compared with control group, immature dendritic cells group and mature dendritic cells group, the average survival time of graft renal in RNA interference RelB treatment group prolonged significantly （P 0.01）. The content of aspartate aminotransferase and total bilirubin in RNA interference RelB treatment group at 7 days aftertransplantation were significantly lower that those in the control group, immature dendritic cells group and mature dendritic cells group （P 0.01）, while the content of aspartate aminotransferase and total bilirubin at 14 days after transplantation in RNA interference RelB treatment group and immature dendritic cells group were slightly decreased,

关 键 词：转录因子RelB 树突状细胞 RNA干扰 肝移植 免疫耐受 大鼠 

分 类 号：R617[医药卫生—外科学]