环孢素A纳米粒滴眼液抗大鼠角膜移植术后排斥反应的实验研究

The prevention effect of cyclosporine A nano-particle eye drop on cornea immune rejection in a rat penetrating cornea transplantation model

目的探讨环孢素A纳米粒滴眼液对大鼠同种异体角膜移植术后角膜排斥反应的抑制作用。设计实验研究。研究对象Lewis大鼠50只,F344大鼠25只。方法 Lewis大鼠作为穿透性角膜移植受体分5组各10只,A组为阴性对照组,给予环孢素A纳米粒滴眼液基质点眼,B组为普通环孢素滴眼液组,C、D、E组分别为0.5%、1%、2%环孢素A纳米粒滴眼液组。F344大鼠为供体。术后各组滴用相应的滴眼剂,每日3次。术后14天内每日、14天后每2日拍摄角膜照片,观察至术后28天。术后14天取大鼠角膜组织行组织病理学检查。主要指标角膜植片存活时间、角膜排斥反应指数(RI)、角膜组织病理改变。结果 A、B、C、D、E组角膜植片存活时间分别为8.1±1.37天、12.5±4.72天、12.11±4.46天、13.11±4.65天和13.56±3.88天(F=2.916,P=0.032)。普通环孢素滴眼液组,0.5%、1%、2%环孢素A纳米粒滴眼液组与基质组相比,差异具有统计学意义(P均<0.05)。普通环孢素滴眼液组与0.5%、1%、2%环孢素A纳米粒滴眼液组相比,差异无统计学意义(P均>0.05)。A、B、C、D、E组RI分别为7.3±0.67、5.5±1.35、6.11±1.45、5.22±1.48和4.77±1.20(,F=5.782,P=0.001)。普通环孢素滴眼液组、0.5%、1%、2%环孢素A纳米粒滴眼液组与基质组相比,RI有统计学意义(P均<0.05。普通环孢素滴眼液组与0.5%、1%、2%环孢素A纳米粒滴眼液组比较,差异无统计学意义(P均>0.05)。2%环孢素A纳米粒滴眼液组与0.5%环孢素A纳米粒滴眼液组比较差异具有统计学意义(P=0.03)。结论环孢素A纳米粒滴眼液与普通环孢素滴眼液具有相似的抑制角膜移植术后排斥反应的作用,2%环孢素A纳米粒滴眼液组效果优于0.5%浓度组。

To investigate the prevention effect of cyclosporine A nanoparticle eye drop on cornea immune rejection in a rat experimental model. Design Experimental study. Participants Fifty Lewis rats and twentyfive F344 rats. Method Fifty Lewis rats were divided into 5 groups （group A to group E）, all of which were received penetrating cornea transplantation in the right eyes. The provider were F344 rats. Group A received vehicle eye drop, group B received ordinary cyclosporine eye drop, group C to E received 0.5%, 1% and 2% cyclosporine A nanoparticle eye drop respectively. All the receptor eyes received the eye drops 4 times a day. Cornea were observed with slit lamp and photographs were taken everyday within 14 days after cornea transplantation, and then ob- served every other day until 28 days. The mean survival time and rejection index （RI） were calculated. The corneas were studied pathologically at day 14th. Main Outcome Measures Cornea survival time, rejection index, pathologically observation of cornea. Results The mean survival time in group A, B, C, D, E were 8.1±1.37 days, 12.5±4.72 days, 12.11±4.46 days, 13.11±4.65 days and 13.56±3.88 days respectively（F=2.916, P=0.032）. The survival time in any of group B, C, D, E is longer compared with group A （all P〈0.05）. RI of group A to E was 7.3±0.67, 5.5±1.35, 6.11±1.45, 5.22±1.48 and 4.77±1.20, respectively （F=5.782, P=0.001）. RI in group B, C, D, E is lower compared with group A （all P〈0.05）. No significant difference was found between any of group C, D, E and ordinary cyclosporine eye drop （P=0.297, 0.634, 0.219）. But significant difference was found between 2% cyclosporine A nanoparticle group and 0.5% group （P=0.03）. Conclusion Cyclosporine A nanoparticle eye drop can effectively prevent cornea rejection after penetrating cornea trans plantation. Its effect is similar to ordinary cyclosporine eye drop. The effect of 2% eyclosporine A nanoparticle eye drop was better than 0.5% cyclosporine A nanoparticle eye drop. （Ophthalmol CHN, 2012, 21： 55-59）