摘要
目的研究核因子-κB(nuclear factor-κB,NF-κB)在角膜移植急性免疫排斥反应中的作用。方法建立大鼠角膜移植模型90只,同基因移植组Wistar鼠供体10只,受体20只;同种异体移植组及同种异体移植+环孢霉素A(ciclosporin A,CsA)治疗组,均为Wistar大鼠10只为供体,SD大鼠20只为受体。各组术后不同时间点(3d、7d、12d、18d)测定角膜移植排斥反应指数评分,并于各时间点观察角膜植片病理学变化,检测NF-κB与细胞间黏附分子-1(intercellular adhesion molecule1,ICAM-1)、血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达。结果角膜移植大鼠模型中,在观察期18d内,同基因组无1例出现排斥反应,同种异体组在各时间点的排斥反应指数显著高于同基因组(P<0.05),而同种异体移植+CsA治疗组排斥反应较同种异体移植组明显受到抑制(P<0.05)。免疫组织化学结果显示:NF-κB与ICAM-1、VEGF分布角膜上皮层、基质层及新生血管内皮细胞。在各时间点,同种异体移植组角膜中NF-κB与ICAM-1、VEGF的表达高于同基因移植组(P<0.05),而低于同种异体移植+CsA治疗组(P<0.05)。对比观察发现:NF-κB表达强度与排斥反应指数成正相关(r=0.901,P=0.000),且与下游基因ICAM-1(r=0.833,P=0.000)、VEGF(r=0.935,P=0.000)的表达强度成正相关。结论NF-κB的激活参与角膜移植排斥反应的发生。CsA通过减弱NF-κB核转位和发挥活性,抑制受其调控的多种细胞因子、黏附分子等移植排斥相关因子的表达,从而抑制角膜移植排斥反应的发生发展。
Objective To study the effect of nuclear factor-κB（NF-κB） on corneal transplant rejection.Methods Ninety corneal transplantation model were developed and divided into three groups：GroupⅠ：syngeneic group（10 wistar rats as donors and 20 wistar rats as recipients）;GroupⅡ：allograft group（10 wistar rats as donors and 20 SD rats as recipients）;GroupⅢ：allograft treated with ciclosporin A（CsA） eye drops（10 Wistar rats as donors and 20 SD rats as recipients）.The change of the corneal transplantation rejection index （RI） was observed at different times in each group,postoperative 3 days,7 days,12 days and 18 days respectively.Cellular and morphologic changes of corneal buttons were evaluated by light microscope examination.NF-κB and intercellular adhesion molecule 1（ICAM-1）、vascular endothelial growth factor（VEGF） levels were determined by immunohistochemistry combined with computer-assisted image analysis in corneal graft at different times.Results In corneal transplantation models,corneal RI in allograft group were higher than those in syngeneic group（P〈0.05）,and corneal RI in allograft with CsA group were lower than those in syngeneic group（P〈0.05）.NF-κB and ICAM-1、VEGF were expressed in corneal epithelial cells,keratocytes and corneal neovascular endothelial cells in the cornea graft.The expressions of NF-κB and ICAM-1、VEGF in allograft group were higher than those in syngeneic group（P〈0.05）,and lower than those in allograft＋CsA group（P〈0.05）.The location of NF-κB expression was similar to ICAM-1（r=0.833,P=0.000）,VEGF（r=0.935,P=0.000）,and had nicely correlations.Clinical observation showed the expression of NF-κB was significantly correlated with RI（r=0.901,P=0.000）.Conclusion The activation of NF-κB may play a potential role in the development of corneal transplant rejection.CsA can inhibit the expression of associated transplant rejection factor,and prevent the occurrence of corneal transplant rejection.
出处
《眼科新进展》
CAS
2007年第11期816-820,共5页
Recent Advances in Ophthalmology
基金
广东省自然科学基金资助(编号:032839)~~
关键词
移植排斥
核因子-ΚB
细胞黏附分子
血管内皮生长因子
免疫组织化学
环孢霉素A
鼠
corneal transplantation
nuclear factor-κB
cell adhesion molecules
vascular endothelial growth factor
immunohistochemistry
ciclosporin A
rat
