趋化因子RANTES和受体CCR5在心脏移植慢性排斥反应中的表达  

Expression and significance of RANTES and CCR5 in chronic rejection of cardiac allografts

作　　者：张远浩[1] 宋光民[1] 赵文杰[1] 白宵[1] 张敬国[1] 赵鑫[1] 

机构地区：[1]山东大学齐鲁医院心外科,济南250012

出　　处：《山东大学学报（医学版）》2012年第6期38-41,45,共5页Journal of Shandong University:Health Sciences

基　　金：山东省科技攻关计划资助项目(2010GSF10246);山东省自然科学基金资助项目(Y2007C056)

摘　　要：目的探讨调节活化正常T细胞表达和分泌因子(RANTES)及其受体CCR5在心脏移植慢性排斥反应中的表达及意义。方法健康近交系Sprague-Dawley(SD)大鼠为受者,Wistar大鼠为供者,采用"套管连接技术"建立颈部心脏移植的实验模型。将SD大鼠随机分为3组:A组(n=12)供、受者均未采用任何治疗;B组(n=12)移植手术后使用环孢素A(CsA)10 mg.kg-1治疗受者,术后2～3个月采集移植心脏;C组(n=24)使用供者脾细胞(SPC)及环磷酰胺(CP)预处理受者,其中12只在术后15～60 d采集移植心脏(C1组),另外12只术后至少观察半年(C2组)。采用H-E染色观察移植心脏组织排斥反应病理改变程度,Van Gieson染色观察移植心脏血管病变(CAV)的血管狭窄程度,免疫组化检测RANTES和CCR5的表达水平。结果 SPC和CP预处理后,移植心脏的存活时间明显延长,RANTES和CCR5在冠状血管和心肌组织中呈低水平表达,移植心脏血管病和心肌纤维化明显减轻;而在急性排斥反应和CsA治疗的移植心脏组织中,RANTES和CCR5的表达水平明显增强,差异有统计学意义(P<0.05)。结论移植心脏组织中RANTES和CCR5的表达水平与移植排斥反应的程度密切相关。Objective To investigate expressions of regulation upon activation of normal T-cell expressed and secreted （RANTES） and CCR5 in the chronic rejection of cardiac allografts. Methods Cervical cardiac transplantation by cuff- technique was performed from Wistar rats to Sprague-Dawley （SD） rats. The SD rat recipients were randomly divided into 3 groups： （A） （n = 12） Both the recipients and the donors were without any treatment. （B） （n = 12） The recipi- ents were treated with 10 mg/kg^1 cyclosporine A after transplantation and euthanized 2 to 3 months later. （C） （n =24 ） The Sprague-Dawley rat recipients were pretreated with donor splenocyte （SPC） and cyclophosphamide （CP）. Half were euthanized 15-60 days after transplantation（ C1 ） and the other half were monitored for at least 6 months after trans- plantation（C2）. Pathological change of the allograft caused by the rejection was observed by H-E staining. Cardiac al- lograft vasculopathy （CAV）was observed by Van Gieson staining. Expressions of RANTES and CCR5 were monitored by immunohistochemistry. Results Pretreatment of animals with SPC and CP induced long-term cardiac allograft sur- vival. Immunohistochemical staining demonstrated a low level of RANTES and CCR5 expressions in the cardiac allograft muscles and coronary arteries in Group C. In contrast, expressions of RANTES and CCR5 in the cardiacallografts of Groups A and B were significantly higher than those in Group C （ P 〈 0.05 ）. The CAV and myocardial fi- brosis were dramatically reduced in Group C compared with those of Groups A and B （ P 〈 0.05）. Conclusion Expressions of RANTES and CCR5 in cardiac allografts may play an important role during the development of chronic rejection.

关 键 词：移植心脏血管病 心肌纤维化 趋化因子及趋化因子受体 大鼠 

分 类 号：R654[医药卫生—外科学] R332[医药卫生—临床医学]