两性霉素B脂质体滴眼液对兔曲霉菌性角膜溃疡角膜内皮细胞毒性观察

An observation of the toxicity of topical application of amphotericin B liposomal on corneal endothelial cell of aspergillus keratomycosis in a rabbit model

目的:观察不同浓度两性霉素B脂质体(AmBL)滴眼液对兔曲霉菌性角膜溃疡模型内皮细胞的影响,初步探讨临床上两性霉素B脂质体滴眼液治疗曲霉菌性角膜溃疡的安全药效浓度。方法:30只健康成年新西兰白兔,采用角膜"#"形划痕法制作实验性曲霉菌性角膜溃疡模型,随机分为3组,每组10眼。A组应用0.50%AmBL滴眼液点眼;B组应用0.25%滴眼液点眼;C组为生理盐水对照组。每天6次。3、7、10、15d观察疗效,并用共聚焦显微镜观察角膜内皮细胞形态,检测内皮细胞平均密度、内皮细胞面积变异系数、六边形细胞百分率。结果:造模3d内皮细胞平均密度,变异系数,六边形细胞百分率各组间差异无显著性;治疗3d后A,B两组与对照组相比溃疡较前局限,结膜充血和角膜水肿减轻,用药后7d溃疡内皮斑减轻,坏死组织脱落,新生血管出现,平均10d角膜水肿消失,瘢痕形成,各项指标均优于对照组。点药后3d内皮细胞平均密度、变异系数、六边形细胞百分率A组与B组比较差异无显著性,与C组比较差异有显著性,7、10、15d后A、B两组间差异出现显著性,A组内皮细胞肿大,多形性,边界中断,形态模糊,较B组显著。结论:两性霉素B脂质体对曲霉菌性角膜溃疡治疗有效,0.25%与0.50%滴眼液相比治疗效果相同,但对角膜内皮影响较小。

Objective The aim of this study was to evaluate the toxicity of amphotericin B liposomal（AmBL） topical application on corneal endothelial cells in the aspergillus keratomycosis in a rabbit model.Methods Thirty New Zealand White rabbits model of aspergillus keratitis were randomized into three groups（groups A,B and C）.Treatments included a control plus 0.50% AmBL（groups A）,0.25% AmBL（groups B）and NS（groups C）.Rabbits were instilled topical eye drops six times a day.After 3,7,10 and 15 days treatment,confocal microscopy was performed to examine the morphology of corneal endothelial cell.Results There were no significant different in endothelial cell density,percentage of hexagonal and coefficient of variation in three groups after modeling.After 3 days in both treatment groups,the corneal ulcers limitated and conjunctival hyperemia and corneal edema reduced.In A,B group,average 10d corneal edema disappeared and scar formed.The difference was singifficantly compared with control group.After 3 days of treatment,endothelial cell density,coefficient of variation of cell size,and percent of hexagonal cells of corneal endothelial cells were no singifficantly difference in A,B group.But after 7,10 and 15 d treatment,There were significant differences in cell morphology in group A and B.Conlusions Intracameral amphotericin B may be an effective adjunctive treatment of aspergillus keratomycosis.Compared with 0.50% AmBL,0.25% AmBL has the same effect,but little effect on the corneal endothelium.