摘要
目的 观察单核细胞、NK细胞和T细胞在猪 猕猴延迟性异种移植排斥反应 (DXR)中的作用。方法 建立湖北白猪 云南猕猴的腹腔异位心脏移植模型 ,实验分为 2组 :对照组 (n =5 ) ,不使用中华眼睛蛇毒因 (Y CVF) ;实验组 (n =4)应用Y CVF完全清除受者体内补体。 2组受体猴均采用环孢素A(CsA) ,环磷酰胺 (CTX)和甲基强的松龙 (MP)三联免疫抑制治疗。免疫组织化学方法检测移植心组织中细胞间黏附分子 (ICAM ) 1、肿瘤坏死因子 (TNF) α、单核细胞、NK细胞和T细胞的表达。结果 对照组 3个移植心在 15~ 60min内发生超急性排斥反应 (HAR) ,另 2个分别存活 2 2h及 6d ,移植心均未见明显的炎性细胞浸润及ICAM 1和TNF α的表达。实验组移植心存活时间分别为 8、10、13和 13d ,移植物浸润细胞中可见大量的单核细胞 (5 0 % ) ,少量的NK细胞 (8%~ 10 % ) ,CD4+ T细胞 (15 % )和CD8+ T细胞 (2 5 % )。移植物血管内皮细胞表面出现ICAM 1的表达上调 ,移植物间质中出现TNF α的表达增加。结论 单核细胞、NK细胞和T细胞介导的移植物损伤 ,在应用Y CVF处理的猪 猕猴DXR发生中发挥重要作用。
Objective To investigate the role of macrophages,NK cells,and T cells in delayed xenograft rejection of pig-to-rhesus monkey cardiac transplantations.Methods Heterotopic xenogeneic heart transplantation in the abdominal cavity was performed using piglet as donors.The experiment was devided into 2 groups:control group (n=5):without a high activity cobra venom factor (Y-CVF) treatment;experimental group (n=4):complete complement depletion was achieved in the recipients treated with Y-CVF.The recipients were immunosuppressed with a combination of cyclosporine A,cyclophosphamide and steroids.The graft were examined histopathologically and immunohistochemically for necrosis factor-alpha (TNF-alpha),intercellular adhesion molecule-1 (ICAM-1),CD 57 (NK cells),CD 68 (macrophages),CD 4 and CD 8.Results The survival time of 3 xenografts in control group was 15 to 60 min and hyperacute rejection (HAR) occurred,while the remaining 2 xenografts survived 22 h and 6 days respectively,and there was no significant cellular infiltration and the expression of ICAM-1 and TNF-alpha in HAR xenografts.But in the experimental group,the xenografts survived 8,10,13,13 days respectively and DXR occurred in all the grafts.Large numbers of macrophages (50%) were found to infiltrate the entire xenograft.8% to 10% of natural killer cells,15% of CD 4+T cells and 25% CD 8+T cells were detected also.ICAM-1 was up-regulated in the graft endothelial cells and TNF- alpha in the interstitial tissue was demonstrated in the rejected heart.Conclusion Cell-mediated rejection is an important feature in the DXR of pig-to-rhesus monkey cardiac transplantations after Y-CVF therapy.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2004年第3期363-364,F003,共3页
Chinese Journal of Experimental Surgery
基金
国家"十五"高新技术研究发展计划 (863计划 )资助项目(2 0 0 1AA2 1 60 71 )