目的 評(píng)估結(jié)膜下注射伏立康唑?qū)ν醚劢悄さ陌踩?尋找兔眼結(jié)膜下注射伏立康唑的安全劑量。
方法 健康成年新西蘭白兔25只,按體質(zhì)量隨機(jī)分為對(duì)照組、伏立康唑(50、100、200、400 μg)組。對(duì)照組結(jié)膜下注射0.1 mL生理鹽水,伏立康唑組均結(jié)膜下注射0.1 mL伏立康唑注射液,分別含50、100、200、400 μg注射用伏立康唑。1次/d,連續(xù)給藥5 d。分別于給藥前及末次給藥后的第1、7、14天,裂隙燈和直接眼底鏡觀察眼部基本情況。末次給藥后第1、7、14天觀察角膜各層細(xì)胞的變化,計(jì)數(shù)角膜內(nèi)皮細(xì)胞的數(shù)量,并測(cè)量角膜厚度。末次給藥后第14天摘取實(shí)驗(yàn)眼眼球,HE染色,觀察角膜組織形態(tài)。
結(jié)果 共聚焦顯微鏡及HE結(jié)果顯示,伏立康唑50、100 μg組給藥后,角膜各層細(xì)胞未見異常;伏立康唑200、400μg組給藥后,角膜各層細(xì)胞不同程度異常。各給藥組內(nèi)皮細(xì)胞計(jì)數(shù)、角膜厚度與對(duì)照組比較,差異均無(wú)統(tǒng)計(jì)學(xué)意義。
結(jié)論 兔眼結(jié)膜下注射≤100g的伏立康唑?qū)悄な前踩摹?/div>
[Key word]
[Abstract]
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≤100μg.
[中圖分類號(hào)]
[基金項(xiàng)目]
天津市衛(wèi)生局科技基金項(xiàng)目(2013KY36)