FK506纳米粒对大鼠角膜移植排斥反应的影响  

Effects of the FK506 nanoparticles delivery system on a penetrating keratoplasty rejection model in the rat

作　　者：费文雷[1] 陈家祺[1] 庞志清[2] 骆新兰[3] 刘永民 王铮[1] 袁进[1] 蔡秀玲[3] 

机构地区：[1]中山大学中山眼科中心,广州510160 [2]中山大学医学院 [3]广东省人民医院病理科 [4]广东省视觉眼科学研究所

出　　处：《眼科研究》2006年第2期156-159,共4页Chinese Ophthalmic Research

基　　金：卫生部科研基金(20013955);广东省科技计划项目基金(2002C30902);广州市科技攻关项目基金(2003Z3-E0351)资助

摘　　要：目的观察FK506纳米粒对大鼠角膜移植排斥反应模型的作用。方法Wistar大鼠为供体,对70只SD大鼠行异体穿透角膜移植,14只SD大鼠接受自体角膜移植,观察不同组别植片的存活时间及免疫病理改变。结果各组植片存活时间分别为Ⅰ组(不用药)(7.90±1.20)d;Ⅱ组(PLGA)(8.44±0.88)d;Ⅲ组(0.05%地塞米松)(10.44±1.42)d;Ⅳ组(0.05%FK506)(11.60±2.55)d;Ⅴ组(0.01%FK506纳米胶体)(15.09±4.81)d。Ⅰ组与Ⅲ、Ⅳ、Ⅴ组植片存活时间有显著统计学差异。Ⅴ组与Ⅲ、Ⅳ组植片存活时间也有显著统计学差异。排斥反应的植片有多量CD8+、中等量CD4+T细胞浸润和巨噬细胞浸润,ICAM、VEGF等免疫分子与炎症和排斥反应程度吻合。Ⅴ、Ⅳ组植片的炎性细胞较少。结论FK506局部滴眼可延长植片存活时间,FK506纳米胶体较FK506滴眼液能维持更长时间的植片透明。Objective FK506 is thought to have the inhibiting ability to corneal reject. We were to evaluate the efficacy of topical nanoparticles containing FK506 as the drug delivery system on a penetrating keratoplasty rejection in the rat. Methods Eighty-four Spragru-Dawley （SD） rats received corneal allografts from Wistar donors or autograft and were divided into 6 groups. Group Ⅰ without any treatment; group Ⅱ was treated with empty nanoparticles solution; group Ⅲ received 0.05% Dexamethasone eye drops; In group Ⅳ 0.05% FK506 was applied locally;and group Ⅴ received 0.01% FK506-loaded nanoparticles; group Ⅵ was autografted SD rats and was not treated with FK506. FK506 was topically used two times daily for 28 days in group Ⅱ to group Ⅳ. Grafts were examined using slit-lamp and the mean survival time was calculated. Rats eyes were enucleated for histological and immunohistochemical analysis. Results Mean graft survival time was 7.90±1.20 days in group Ⅰ, 8.44±0.88 days in group Ⅱ, 10.44±1.42 days in group Ⅲ, 11.60±2.55 days in group Ⅳ, 15.09±4.81 days in group Ⅴ, and more than 28 days in group Ⅵ. There was a statistically significant difference in survival time between group Ⅴ and other allografts group （P≤0.01）. Macrophages, CD4 and CD8 positive cells were found in the transplanted areas, and VEGF and ICAM1 expression were demonstrated after corneal allograft transplantation. At the same time point, the corneas received FK506 nanoparticles showed a limited inflammatory response characterizing by reduction in the number of infiltrating of inflammatory cells. Conclusion 0.05% FK506 eye drops delay corneal rejection, and FK506 loaded nanoparticles prolongs corneal allograft survival compared with 0.05% FK506 and 0.05% Dexamethasone eye drops.

关 键 词：FK506 纳米微粒 角膜移植 大鼠 

分 类 号：R779.65[医药卫生—眼科]