结膜下注射伏立康唑对兔眼角膜的安全性评价

Safety evaluation of rabbit corneas with subconjunctival injection of voriconazole

目的评估结膜下注射伏立康唑对兔眼角膜的安全性,寻找兔眼结膜下注射伏立康唑的安全剂量。方法健康成年新西兰白兔25只,按体质量随机分为对照组、伏立康唑(50、100、200、400μg)组。对照组结膜下注射0.1 m L生理盐水,伏立康唑组均结膜下注射0.1 m L伏立康唑注射液,分别含50、100、200、400μg注射用伏立康唑。1次/d,连续给药5 d。分别于给药前及末次给药后的第1、7、14天,裂隙灯和直接眼底镜观察眼部基本情况。末次给药后第1、7、14天观察角膜各层细胞的变化,计数角膜内皮细胞的数量,并测量角膜厚度。末次给药后第14天摘取实验眼眼球,HE染色,观察角膜组织形态。结果共聚焦显微镜及HE结果显示,伏立康唑50、100μg组给药后,角膜各层细胞未见异常;伏立康唑200、400μg组给药后,角膜各层细胞不同程度异常。各给药组内皮细胞计数、角膜厚度与对照组比较,差异均无统计学意义。结论兔眼结膜下注射≤100μg的伏立康唑对角膜是安全的。

Objective To evaluate the safety of rabbit corneas with subconjunctival injection of voriconazole, and explore a safe range of antibiotic dose. Methods According to body weights, total 25 healthy rabbits were randomly divided into control group, and voriconazole（50, 100, 200, and 400 μg） groups. The eyes of control group received subconjunctival injection of 0.1 mL balanced salt solution（BBS）, and those treatment groups received 0.1 mL injection containing Voriconazole for injection 50, 100, 200, and 400 μg, respectively. Every rabbit received five injections, once daily. Before the administration and 1, 7, and 14 d after the last injection, basic situations of the eyes were observed with slit lamp biomicroscopy and direct ophthalmscopy. Ultrastructures of the corneas were detected in vivo observation 1, 7, and 14 d after the last injection, respectively, and endothelial cell counts and corneal thicknesses were performed at the same time using confocal microscopy. Fourteen days after the last injection, pathological observations were carried out for corneal morphology. Results Subconjunctival injection of voriconazole in the rabbits at doses of 50 and 100 μg, there was no abnormality in corneal cells, but at doses of 200 and 400 μg, the rabbits showed edema cornea, exfoliation of corneal epithelium and abnormities in ultrastructures. However, there was no significant difference in endothelial cell counts and corneal thickness with those of control group at any time points. Conclusion It is safe for corneas of rabbit subconjunctival injection of voriconazole at the dose ≤100 μg.