抗肿瘤坏死因子-α单克隆抗体抑制大鼠角膜移植排斥反应  

Inhibition of anti-tumor necrosis factor-alpha monoclonal antibody on rat corneal graft rejection

作　　者：张士胜[1] 李贵仁[2] 廖华萍[1] 王康孙[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院眼科上海瑞视眼科,中国上海市200025 [2]潍坊医学院附属医院眼科中心,中国山东省潍坊市261031

出　　处：《国际眼科杂志》2009年第2期257-259,共3页International Eye Science

基　　金：中国上海市重点学科建设项目资助(No.S30205)~~

摘　　要：目的:探讨肿瘤坏死因子-α(TNF-α)在角膜移植免疫排斥反应中的作用以及抗TNF-α单克隆抗体(TNF-α mAb)对排斥反应的抑制作用。方法:以近交系大鼠30只制作穿透性角膜移植模型(F344→Lou),随机等分入移植治疗组(每日结膜下注射0.5g/L抗TNF-α mAb 0.1mL)和移植模型组(结膜下注射等量生理盐水)。利用酶联免疫吸附实验(ELISA)技术分别检测术后3,7d及发生排斥反应时大鼠外周血清中TNF-α的水平,并观察移植角膜的组织病理学变化及植片存活情况。结果:角膜移植术后早期各组大鼠血清TNF-α浓度均有升高,与移植治疗组相比,移植模型组升高速度更快,水平更高(P<0.05);但当发生排斥反应时,二者已无显著性差异(P>0.05)。移植模型组大鼠植片存活时间为10.2±1.9d,而抗体治疗组平均13.8±2.2d,二者相比差异有显著性(P<0.01)。结论:TNF-α在角膜移植免疫排斥反应中发挥一定作用。动态检测外周血TNF-α浓度有助于预测、诊断排斥反应。应用抗TNF-αmAb治疗可部分延长植片存活时间。AIM： To investigate the role of tumor necrosis factor- alpha （TNF-a） in the allograft rejection of rat corneal transplantation and to evaluate the inhibition effect of anti- TNF-a monoclonal antibody （mAb） on it. METHODS. After received allogeneic grafts （F344→Lou rat）, 30 inbred Lou rats were divided equally into two groups, the transplantation model group and the transplantation treatment group. While the treatment group were treated daily by subconjunctival injection of anti-TNF-a mAb （0. l mL, 0. 5 g/L）, the model group received the same volume injection of physiologic saline. Then, the serum levels of TNF-a were measured by using enzyme linked immunosorbent assay （ELISA） at 3 and 7 day, and the time when graft rejection occurred after corneal transplantation respectively. The corneal histopathological changes and the allograft survival times were also observed. RESULTS： The serum levels of TNF-α in all rats elevated in the early stage after surgery, especially to the model group. Anti-TNF-α mAb decreased the levels and made them increase slowly （P 〈 0. 05）. When the rejection occurred, the significant difference between the two groups didn＇t exist any more （ P 〉 0.05）. The treatment group had a significant delay in corneal allograft rejection with mean survival time of 13.8± 2.2 days vs10.2±1.9 days for the model group （P〈0.01）. CONCLUSION. TNF-α may play an important role in the pathogenesis of corneal allograft rejection. Sequential determinations of serum TNF-α after operation may be of value in the prediction and diagnosis of acute rejection. Anti-TNF-α antibody treatment can prolong the allograft survival time to some extent.

关 键 词：角膜移植 排斥反应 肿瘤坏死因子-Α 单克隆抗体 大鼠 

分 类 号：R779.65[医药卫生—眼科]