急性排斥期大鼠角膜移植物肿瘤坏死因子相关凋亡诱导配体及死亡受体4表达变化与环孢素A的干预

Cyclosporin A effects on expressions of tumor necrosis factor-related apoptosis-inducing ligand and death receptor 4 in rat corneal allografts during acute rejection phase

目的:研究提示,肿瘤坏死因子相关凋亡诱导配体及其死亡受体4可能参与角膜移植免疫排斥反应。观察免疫抑制剂环孢素A对急性排斥期角膜移植物肿瘤坏死因子相关凋亡诱导配体及其受体死亡受体4表达的影响。方法:实验于2007-07/10在南方医科大学珠江医院中心实验室完成,对动物处置方法符合动物伦理学要求。选用Wistar大鼠18只为供体,SD大鼠36只为受体,钻取供体双眼角膜植片,于受体右眼行穿透性角膜移植术;另取5只Wistar大鼠做正常对照。按随机数字表法将受体大鼠分为2组(n=18),即生理盐水组及环孢素A组,术后药物滴眼,2次/d,1滴/次,连用2周。应用免疫组织化学法检测急性排斥期角膜植片肿瘤坏死因子相关凋亡诱导配体及死亡受体4表达情况。结果:36只受体大鼠全部进入结果分析。①肿瘤坏死因子相关凋亡诱导配体及死亡受体4在正常角膜均有表达,主要分布于上皮层,在基质层及内皮层有少量表达。②环孢素A组和生理盐水组大鼠角膜植片各层肿瘤坏死因子相关凋亡诱导配体及死亡受体4表达均增高,生理盐水组增高尤为明显。结论:肿瘤坏死因子相关凋亡诱导配体及死亡受体4的表达参与角膜移植免疫排斥反应的发生,环孢素A可通过下调其表达抑制角膜移植免疫排斥反应。

AIM： Tumor necrosis factor-related apoptosis-inducing ligand （TRAIL） and death receptor 4 （DR4） participate the immunological rejection in corneal transplantation, The study aimed to investigate the influence of cyclosporin A on expression of TRAIL and its DR4 in corneal allografts, METHODS： Experiments were performed at the Central Laboratory of Zhujiang Hospital, Southern Medical University from July to October 200% The protocol was in accordance with animal ethical standards. Eighteen Wistar rats were selected as donors, whereas thirty-six SD rats were selected as receptors. Corneas of both eyes were obtained by drilling from donors, and penetrating right eye corneal transplantation was performed. Another five Wistar rats were selected as controls. Receptor rats were randomly divided into saline group （n=18） and cyclosporin A group （n=18）, Drugs were dropped into eyes after the surgery, twice a day, once one drop for 2 weeks. Immunohistochemistry was used to detect the expression of TRAIL and DR4 in corneal allografts during allograft rejection. RESULTS： A total of 36 rats were included in the final analysis. （1）TRAIL and DR4 were detected on normal cornea, mainly on the epithelium, with modest staining in the stroma and endothelium, （2）Expressions of TRAIL and DR4 were increased in the cyclosporin A group and the saline group, especially in the saline group. CONCLUSION： TRAIL and its receptor DR4 may be related to the immunologic process of corneal graft rejection, and cyclosporin A suppresses postoperative immunologic rejection in keratoplasty.