白细胞介素17中和性抗体对角膜移植排斥反应的抑制作用  

Inhibitory effect of neutralizing interleukin-17 antibody on corneal allograft rejection

作　　者：陈雪冬[1] 赵士勇[2] 唐先玲[1] 葛红岩[1] 刘平[1] 

机构地区：[1]哈尔滨医科大学附属第一医院眼科医院,150001 [2]哈尔滨医科大学附属第二医院胆道胰腺外科,150086

出　　处：《中华实验眼科杂志》2012年第10期897-901,共5页Chinese Journal Of Experimental Ophthalmology

基　　金：黑龙江省教育厅基金项目（11551267）

摘　　要：背景白细胞介素17（IL-17）是一种促炎性细胞因子，在多种器官移植免疫排斥反应和自身免疫性疾病中发挥致病作用。IL-17拮抗剂在器官移植排斥反应中的作用被广泛研究，但其对角膜移植后排斥反应防治作用的研究较少。目的探讨抗小鼠IL-17单克隆抗体对小鼠角膜移植排斥反应的抑制效果。方法选取8～10周龄C57BL／6小鼠25只和BALB／c小鼠50只，将直径2min的C57BL／6小鼠双眼中央角膜作为供体角膜移植到50只BALB／c小鼠右眼角膜植床上，11，0尼龙线间断缝合8针，建立小鼠角膜移植模型。将建立的40只角膜移植小鼠模型按随机数字表法随机分为2个组，术后腹腔内分别注射小鼠IL-17中和性抗体（IL-17中和性抗体组）或同型对照抗体（同型对照抗体组），并于术后不同时间点根据Plskova等的标准对受体角膜植片的炎症反应情况进行评分，≥5分为发生排斥反应。应用免疫荧光组织化学法检测受体植片炎性细胞的浸润；用逆转录PCR法对植片中的炎性细胞进行定量；应用ELISA法分析两组受体小鼠Th1、Th2和Th17相关细胞因子在脾脏中的表达情况。结果与同型对照抗体组相比，IL-17中和性抗体可以提高角膜植片的存活率（P〈0．05）。IL-17中和性抗体组受体植片中性粒细胞、CD4＋T淋巴细胞和CD8＋T淋巴细胞mRNA含量分别为2．22±0．10、1．64±0．04、1．32±0．10，明显低于同型对照抗体组的3．61±0．08、2．69±0．06、2．17±0．04，差异均有统计学意义（P=0．000、0．000、0．000）。同型对照抗体组受体小鼠脾脏中γ-干扰素（IFN-γ）、IL-12p40和IL-17质量浓度分别为（741．48±10．51）、（1156．90±69．93）、（366．13±7．93）ng／L，明显高于IL-17中和性抗体组的（529．80±13．83）、（539．58±10．74）、（173．70±8．11）ng／L，差异均有统计学意义（P=0．000、0．001、0．000）。结论中�Background Interleukin-17 （IL-17）is a potent pro-inflammatory cytokine and plays a pathogenic role in autoimmune disease. It was confirmed that IL-17 is implicated in allograft rejection of many transplanted organs. Recent studies have focused on the effect of IL-17 antagonists on allograft rejection. Objective This study aimed to investigate the inhibitory effect of anti-mouse IL-17 monoclonal antibody（mAb）on corneal allograft rejection. Methods Twenty-five 8 to 10-week-old C57BL/6 mice and 50 BALB/c mice were collected. Donor cornea grafts with 2 mm diameter from 25 C57BL/6 mice was transplanted to 50 eye of BALB/c mice to establish a model of corneal transplantation. The recipients were randomized into 2 groups,and neutralizing mouse IL-17 antibody or isotype control antibody was intraperitoneally injected immediately after transplantation for experimental treatment,respectively. Allografts were scored clinically at appropriate time points after treatment based on Plskova criteria,and ≥5 was confirmed as rejection. Infiltrating ceils in corneal graft were detected qualitatively and quantitatively by immunohistochemistry and reverse transcription-PCR separately. The cytokine levels of T helper type 1 （Thl） ,Th2,and Thl7 in recipients＇ spleen were analyzed by ELISA. The use of the animals followed the Statement of ARVO. Results Compared with the isotype control antibody group,the survival of grafts was improved in the IL-17 mAb group（ P〈0.05 ）. The levels of neutrophile granulocyte mRNA, CD4＋ and CD8＋ T lymphotes mRNA were 2.22± 0. 10,1.64±0.04 and 1.32±0. 10 in the IL-17 mAb group,showing a significant decline in comparison with those of the isotype control antibody group （ 3.61 ±0.08,2.69±0.06 and 2.17 ±0.04 ） （ P = 0. 000,0. 000,0. 000 ）. Interferon-γ （IFN-γ） , IL-12 p40 and IL-17 concentrations in recipients＇ splenocytes were （ 529.80± 13.83 ） ng/L, （ 539.58 ± 10.74） ng/L and（ 173.70±8.11 ）ng/L in the IL-17 mAb group,and those in the isotype cont

关 键 词：角膜移植术 白细胞介素17 中和抗体 免疫排斥反应 

分 类 号：R779.65[医药卫生—眼科]