环孢霉素A防治LASEK术后角膜雾状混浊的实验研究

Cyclosporin A on preventing and curing Haze after laser subepithelial keratomileusis

目的探讨环孢霉素A(cyclosporin A,CsA)防治兔眼准分子激光上皮瓣下角膜磨镶术(laser subepithelial keratomileusis,LASEK)后角膜上皮下雾状混浊(Haze)的疗效及安全性并与地塞米松比较。方法将48只新西兰白兔随机分成3组:CsA组、生理盐水组和地塞米松组,CsA组、生理盐水组分别在术中一次性应用20g.L-1CsA、生理盐水棉片湿敷术区1min,地塞米松组在术后用1g.L-1地塞米松眼液滴双眼;术后用裂隙灯显微镜观察角膜上皮的愈合及Haze的形成情况,分别于术后1周、1个月、2个月、3个月取兔眼角膜,行光镜、电镜、角膜组织病理学、增殖细胞核抗原检查。结果术后3组间上皮愈合时间无统计学差异(P>0.05)。CsA组和地塞米松组Haze明显轻于生理盐水组,其中CsA组最轻。术后角膜细胞增生显著加重,其中CsA组和地塞米松组明显轻于生理盐水组,且CsA组最轻。光镜、电镜检查:地塞米松和生理盐水组术区角膜上皮细胞过度增生,前基质细胞增生活跃,纤维排列紊乱,细胞外基质明显增多,尤以生理盐水组显著;CsA组上皮细胞和前基质细胞的增生及细胞外基质的合成均受抑制,细胞排列较整齐。3组间均未发现严重眼部并发症。结论环孢霉素A能有效抑制LASEK术后角膜细胞的增殖,减轻角膜Haze,且无明显副作用,可望成为防治角膜Haze的一种新药。

Objective To study the effect and security of cyclosporin A （CaA） on preventing and curing Haze after laser subepithelial keratomileusis as well as comparing CsA with dexamethasone. Methods Fourty-eight New-Zealand rabbits （96 eyes） were divided into three groups at random, CsA group,Normal sodium （NS） group and Dexamethasone group. During the operation,NS and 20 g · L^-1 CsA were respectively placed on cornea for 1 minute in CsA group and NS group. And 1 g · L^-1 dexamethasone eyedrops was used in Dexamethasone group after the operation. Corneal epithelial and Haze were observed by slit lamp microscope after the operation. Corneas were taken out at 1 week,in 1 month,2 months and 3 months respectively,and were examined by light microscope, electron microscope, corneal histopathology, proliferating cell nudlear antigen. Results The healing time of corneal epithelial among three groups had no statistical difference （ P 〉 0.05 ） ; The level of Haze was much higher in NS group than in CsA group and Desamethasone group, of the total, the level of Haze in CsA group was the lowest. The proliferation keratoeyte increased remarkably after operation,and the level in NS group was the highest, The over proliferation of corneal epithelial, the active proliferation of superficial stroma cell, chaotic fiber and over extracellular matrix were detected by light microscope and electron microscope in NS group and Desamethasone group, and that was more obvious in NS group;In CsA group,the proliferation of corneal epithelial and superficial stroma cell and the synthesis of extracellular matrix were prohibited,and keratocyte was in order. Serious complication was not observed in three groups. Conclusion CsA can prohibit the proliferation of keratocyte,reduce Haze effectively and with no obvious complieation,so it may be a kind of new and effective drug to prevent Haze.