方法：将已建立大泡性角膜病变动物模型的9只雌性新西兰白兔随机分为3组：治疗组(n=3)，对照组(n=3)，空白对照组(n=3)。其中治疗组：刮除角膜上皮后，应用0.25%的京尼平浸泡实验眼角膜40min(24℃)； 对照组：刮除角膜上皮后，应用生理盐水浸泡实验眼角膜40min(24℃)； 空白对照组：不进行任何处理。处理后2wk内进行以下检查：裂隙灯检查、中央角膜厚度(CCT)测量、体质量和应激反应评估、组织学检查和利用原位末端转移酶标记技术(TUNEL法)检测基质层细胞凋亡。

结果：与对照组和空白对照组相比，治疗组角膜水肿明显减轻、角膜上皮逐渐修复完整、角膜大泡消失、中央角膜角膜厚度显著下降(P<0.05)、体质量显著增加(P<0.05)。治疗组的实验动物活动性较处理前增加，反抗行为减少，攻击性减低。治疗组角膜基质层胶原纤维排列更为紧致、规则，可见蓝色条索状交联产物。治疗组角膜基质层均偶见凋亡细胞，对照组及空白对照组未明显见凋亡细胞。

结论：京尼平交联治疗可使兔大泡性角膜病变角膜水肿减轻，疼痛症状缓解，其可能的机制为京尼平交联使角膜基质层胶原纤维排列紧密，从而阻止角膜水肿和大泡的形成。

METHODS: Nine female New Zealand white rabbits with bullous keratopathy were used as an experimental model. They were randomized into three groups. Corneas in Group A(treatment group, n=3)were immersed in 0.25% genipin at 24℃ for 40min; those in Group B(control group, n=3)were immersed in 0.9% sodium chloride solution at 24℃ for 40min; and those in Group C(blank control group, n=3)received no treatment. Follow-up examinations were performed within 2wk after treatment, including slit-lamp microscopy, central corneal thickness(CCT), evaluations of body weight and stress responses, histopathological analyses, and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)for detecting stromal cell apoptosis.

RESULTS: Compared to Groups B and C, remission of corneal edema, corneal healing, disappearance of epithelial bullae, a significant decrease in CCT(P<0.05), and a significant increase in body weight(P<0.05)were found in Group A. Animals in Group A became more active and showed less aggression and violent resistance behavior. More regular and dense arrangement of collagen fibers in the corneal stroma and formation of blue strips of cross-linking products were observed in Group A. Cell apoptosis occasionally occurred in the corneal stroma of Group A, while no cell apoptosis was observed in Groups B and C.

CONCLUSION: Genipin cross-linking treatment for bullous keratopathy in rabbits results in remission of corneal edema and relief of pain. We hypothesize that genipin cross-linking strengthens collagen fibers in corneal stroma to avoid the formation of corneal edema and bullae.