环孢素A联合供者骨髓细胞输注延长同种大鼠移植心脏存活时间(英文)  

Combination of cyclosporine A with donor bone marrow cell infusion prolongs heterotopic rat cardiac allograft survival time

作　　者：姜睿[1] 陈江华[2] 何强[2] 吴建永[2] 金娟[2] 

机构地区：[1]泸州医学院附属医院泌尿外科,四川省泸州市646000 [2]浙江大学医学院附属第一医院肾脏病中心,浙江省杭州市310003

出　　处：《中国组织工程研究与临床康复》2008年第18期3583-3586,共4页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：浙江省卫生厅重点基金(2004C23004)~~

摘　　要：背景:同种异体器官移植后需长期使用免疫抑制剂控制机体免疫状态以免发生排斥反应,但免疫抑制治疗使受者的感染发生率增高,诱导移植免疫耐受是解决这一问题的理想方法。在啮齿类动物,已能诱导出长期免疫耐受,其中供者骨髓细胞输注在诱导免疫耐受中具有重要作用。目的:观察环孢素A联合供者骨髓细胞输注对同种大鼠移植心脏存活时间的影响。设计:随机对照动物实验。单位:浙江大学医学院附属第一医院肾脏病中心。材料:实验于2002-03/2004-12在浙江大学医学院实验动物中心完成。选用SPF级近交系雄性Lewis大鼠40只和雄性BN大鼠60只,实验方法符合动物伦理学要求。方法:①制作Lewis→BN大鼠的异位(腹部)心脏移植模型(n=40),将40组动物模型按随机数字表法分为4组(n=10):对照组不进行特别处理;环孢素A组术后连续7d给予环孢素A;联合处理组分别于术中及术后第6天输注供者骨髓细胞,术后连续7d给予环孢素A;供者骨髓细胞组分别于术中及术后第6天输注供者骨髓细胞。另以BN大鼠间的异位(腹部)心脏移植作为BN对照组(n=10)。②观察各组受体大鼠移植心脏的存活时间,检测术后第6天血清白细胞介素2含量以及移植心脏组织中肿瘤坏死因子mRNA表达水平,应用流式细胞仪检测术后第6,12,18天时受体外周血有核细胞中的供体来源细胞、CD3+CD25+细胞、CD4+CD25+细胞的百分比以及共刺激分子CD86表达水平、CD4+CD45RC+/CD4+CD45RC-比率等。主要观察指标:各组受体大鼠移植心脏存活时间、血清白细胞介素2含量及心肌组织中肿瘤坏死因子αmRNA水平、排斥反应分级、外周血有核细胞中的供者来源细胞、CD3+CD25+细胞、CD4+CD25+细胞的百分比及共刺激分子CD86表达、CD4+CD45RC+/CD4+CD45RC-比率等。结果:Lewis大鼠40只及雄性BN大鼠60只全部进入结果分析。①联合处理组大鼠移植心脏存活时间长于�BACKGROUND： To avoid acute rejection, it is necessary to use imunosuppressive drug regimen for long term to control immune state. However, imunosuppressive drug regimen of allogenic organ transplantation increases infection incidence of recipients, and induction of allograft immunological tolerance might be an ideal method for solving these problems. The long-term immunologic tolerance has been able to be induced in the experimental rodent models. Among these protocols, donor bone marrow cell （DBMC） infusion exerts an important role in the induction of allograft immunological tolerance. OBJECTIVE： To investigate effects of combination of cyclosporine A （CsA） with DBMC infusion on heterotopic rat cardiac allograft survival time. DESIDN： A randomized controlled animal experiment. SETTING： Renal Disease Center, First Affiliated Hospital of Zhejing University School of Medicine. MATERIALS： This study was performed at the Laboratory Animal Center, Zhejiang University School of Medicine between March 2002 and December 2005. Inbred male Lewis rats （n=40, serving as donors） and male BN rats （n=60, serving as recipients） of SPF grade were used in this study. The protocol was approved by the Hospital＇s Ethic＇s Committee. METHODS： Forty rats prepared for heterotopic rat cardiac allograft were randomly divided into 4 groups, with 10 rats in each： control group, in which, rats received no treatment, CsA group, in which, rats received CsA infusion for 7 days successively; CsA ＋DBMC group, in which, rats received DBMCs during and 6 days after the surgery and additional 7 successive days of CsA infusion, and a DBMC group, in which, rats received DBMCs infusion during and 6 days after the surgery. In addition, BN rats that received heterotopic rat cardiac allograft served BN controls. The survival time of heteroropic rat cardiac allograft was investigated. Serum interleukin-2 level and tumor necrosis factor-α mRNA expression level in the transplanted cardiac allograft were measured. The percen

关 键 词：心脏移植 移植物存活 环孢菌素 骨髓移植 

分 类 号：R617[医药卫生—外科学]