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单次玻璃体腔注射不同剂量伏立康唑对兔眼角膜和视网膜的影响

The effects on rabbit corneas and retinas after single intravitreal injection of voriconazole at different doses
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摘要 目的观察单次玻璃体腔注射不同剂量伏立康唑对兔眼角膜和视网膜的影响。方法采用随机数字表法将健康新西兰白兔25只随机分为对照组和伏立康唑50、100、200、400μg组,每组各5只兔。对照组兔眼玻璃体腔注射0.1ml生理盐水,伏立康唑各浓度组分别一次性玻璃体腔注射含相应剂量注射用伏立康唑0.1ml。注药前和注药后1、7、14d,使用共聚焦显微镜计数角膜内皮细胞数量、测量角膜厚度;采用全视野视网膜电图检查行最大混合反应(Max-R)检测,记录b波振幅。注药后14d,采用光学显微镜和透射电子显微镜观察兔眼角膜和视网膜组织结构。结果注药前及注药后1、7、14d,伏立康唑各浓度组与对照组兔眼角膜内皮细胞计数(F=0.320、0.291、0.467、0.649)和角膜厚度(F=0.214、0.284、0.360、0.225)比较,差异均无统计学意义(P〉0.05)。注药前及注药后1d,伏立康唑各浓度组与对照组Max-Rb波振幅比较,差异均无统计学意义(F=0.220、0.106,P〉0.05)。注药后7d,伏立康唑200、400μg组Max-Rb波振幅较对照组明显下降,差异有统计学意义(P〈0.05)。注药后14d,伏立康唑200μg组与对照组Max-Rb波振幅比较,差异无统计学意义(P〉0.05);伏立康唑400μg组Max-Rb振幅较对照组明显下降,差异有统计学意义(P〈0.05)。光学显微镜观察发现,对照组和伏立康唑各浓度组兔角膜组织结构均未见损害。对照组和伏立康唑50、100、200μg组兔视网膜各层细胞结构基本正常;伏立康唑400μg组兔视网膜内核层变性、变薄,光感受器细胞层排列紊乱。透射电子显微镜观察发现,对照组和伏立康唑各浓度组兔角膜组织超微结构均未见损害。对照组及伏立康唑50、100扯g组兔视网膜内核层细胞、光感受器细胞内外节超微结构基本正常;伏立康唑200、400μg组兔视网膜内核层和光感受器细胞均有不同程度病变。结论单次玻璃体腔注射≤100μg的伏立康唑对兔眼角膜和视网膜无明显影响;单次玻璃体腔注射200、400μg的伏立康唑对兔眼角膜无明显影响,但视网膜功能和组织形态有不同程度损害。 Objective To observe the effects on rabbit corneas and retinas after single intravitreal injection of voriconazole at different doses. Methods According to the randomization table, 25 healthy rabbits were randomly divided into control group, and voriconazole 50, 190, 200, and 400 μg groups. Therefore, there were 5 rabbits in each group. The eyes of control group received intravitreal injection of 0. 1 ml balanced saline solution, and those treatment groups received 0.1 ml voriconazole injection of corresponding dose. Before the injection and 1, 7, and 14 days after the injection, endothelial cell counts and corneal thicknesses were measured; full-field electroretinogram were performed and b-wave amplitudes in maximal combined reaction (Max-R) were recorded. On 14 days after the injection, histologic structures were observed by light microscope and transmission electron microscope. Results There was no significant difference in endothelial cell counts (F=0. 320, 0. 291, 0. 467, 0. 649) and corneal thicknesses (F=0. 214, 0. 284, 0. 360, 0. 225) with those of control group at any time points (P〉0.05). Before and 1 day after the injection, b-wave amplitudes of each voriconazole group had no significant difference compared with those of control group (F=0. 220, 0. 106; P〉0.05). On 7 days after the injection, b-wave amplitudes decreased significantly at doses of 200 μg and 400 μg (P〈0.05). On 14 days after the injection, there was no significant difference between the the amplitude of 200 μg group and that of control group (P〉0.05). However, the amplitude of the 400 μg group decreased continuously and there was still significant difference (P〈0.05). Light microscopy did not reveal any corneal abnormality in both control group and vorieonazole groups. The retinas were normal except that of the 400 μg group, which had a thinner and degenerated inner nuclear layer and disordered photoreceptor layer. Under transmission electron microscope, there were no ultrastructure damages of corneas in both control group and voriconazole groups, either. The rabbit retinas of the 50 μg and 200 μg group have normal inner nuclear layer and photoreceptor layer, but degrees of changes in both layers were observed in the eyes of 200 μg and 400 μg group. Conclusions There is no obvious effects on rabbit corneas and retinas after single intravitreal injection of voriconazole at he dose less than or equal 100 μg. There are no obvious effects on rabbit corneas at the dose of 200μg and 400μg, while there are damages to the retinas in both functions and histological structures.
出处 《中华眼底病杂志》 CAS CSCD 北大核心 2016年第2期191-196,共6页 Chinese Journal of Ocular Fundus Diseases
基金 天津市卫生局科技基金项目(2013KY36)
关键词 视网膜/药物作用 角膜/药物作用 三唑类/投药和剂量 动物实验 Retina/drug effects Cornea/drug effects- Triazoies/administration dosage Animal experimentation
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参考文献11

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