全身与局部应用伊曲康唑治疗曲霉菌性角膜炎的试验对照研究
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摘要
目的:探讨局部与全身以及联合应用伊曲康唑对实验性兔曲霉菌性角膜炎的疗效研究。
方法:32只新西南大耳白兔刮去右眼角膜中央部上皮,接种烟曲霉菌孢子液于角膜表面,盖亲水性角膜接触镜,48小时后移去。造模成功后随机分为4组。点眼组:自制1%伊曲康唑混悬滴眼液点眼8次/d,每两小时一次;灌胃组:灌胃伊曲康唑胶囊40mg/kg/bid;联合组:点眼同时联合灌胃治疗剂量同前两组;对照组:生理盐水点眼8次/d,每两小时一次。裂隙灯显微镜照相记录观察成模后1, 3, 6, 10, 15, 20, 25d临床病理过程,分别记录临床评分,并发症发生率等。于成模后3, 6, 15, 25d分别行角膜菌丝刮片、真菌培养。于25d全部处死实验兔取角膜组织行病理学检查。
结果:1.比较各组间临床病理过程发现,4组病变早期表现基本一致,治疗第6d后3治疗组在各时间点从病理改变严重程度上较对照组有明显的减轻,病程长度也叫对照组有明显的缩短,治疗低15d后,点眼组、联合组的临床病理表现均较灌胃组轻,但点眼组与联合组之间没无明显差异。
2.治疗第1, 3d,各组临床评分比较无统计学差异,治疗第6d后,3治疗组临床评分均低于对照组且有统计学差异(P<0.01, Tukey HSD test),治疗第15d后,点眼组和联合组临床评分均低于灌胃组且差异有显著性(P <0.05, Tukey HSD test),但点眼组与联合治疗组比较则无显著差异(P>0.05, Tukey HSD test)。
3. 3治疗组前房积脓、角膜穿孔、角膜新生血管化等并发症发生率明显低于对照组且差异有显著性(P<0.01, Fisher’s exact test)。角膜组织刮片真菌阳性培养率在治疗后第6d明显低于对照组且差异有显著性(P<0.05, Fisher’s exact test),但第15, 25d真菌培养均为阴性。结论:1.我们所采用的改良角膜接触镜法对于实验性曲霉菌性角膜炎模型的制备有很高的成功率,本法可以用于曲霉菌性角膜炎模型的制备。
2.从本试验结果来看,局部和全身以及联合应用伊曲康唑对于实验性烟曲霉菌性角膜炎有良好的疗效。点眼组、联合组在治疗后期效果均优于灌胃组,但点眼组与联合组间没有明显差异,提示曲霉菌性角膜炎的治疗应以局部用药为主,全身用药并非必须。
Objective: To investigate the therapeutic role of topical, oral and combine itraconazole treatment using a rabbit model of Aspergillus fumigatus keratitis.
Methods: The epithelium was removed from the central cornea and a inoculum of Aspergillus fumigatus blastoconidia was placed on the corneal surface and covered with a soft contact lens. Forty-eight hours later, the thirty-two rabbits were randomly divided into four groups. Topical group eight rabbits were treated with topical itraconazole (1%, eight times daily), oral group eight rabbits received oral itraconazole (40mg/kg/bid), combine group eight rabbits were treated both topical itraconazole (1%, eight times daily) and oral itraconazole (40mg/kg/bid), untreated controls eight rabbits. The eyes were examined and photographed with a slit-lamp 1, 3, 6, 10, 15, 20 and 25 days after inoculation and an observer graded the corneas in a masked fashion. Corneal scraping, cultures were taken on days 3, 6, 15 and 25 for fungus growth.
Results: 1. Comparing the process of clinical pathology found that four groups consistent performance on 1 to 3 days. In the treated 6 day after, the three treatment groups in various points had significant lower the pathological changes and the course period than the control group. After day 15, the topical and combine groups had significant lower than oral groups, but no difference between topical and combine groups.
2. At the beginning of treatment, 1 to 3 days, the slit-lamp scores did not differ among four groups. However, after days 6 the three treated groups had statistically significant lower scores compared to the untreated controls (P<0.01). On day 15 the topical and combine classes had statistically significant lower marks compared to the oral groups (P<0.05), but no distinguished difference was observed between topical and combine groups at any examination point.
3. Three treated groups, complications such as hypopyon, corneal perforation and corneal neovascularization rate was significantly lower than the control group and there was a significant difference (P<0.01). On day 6, there were significantly lower positive fungal cultures in three treatment groups compared to the control (P<0.05). However, all cultures were negative on days 15-25.
Conclusions: 1. We improved the method of experimental fungal keratitis model which has a high rate of success used by soft contact lens, the method can be used for the model of fungal keratitis.
2. Our study showed that topical, oral and combine itraconazole were effective in lessening the severity of fungal keratitis in a rabbit model and should be considered effective treatment alternatives in the therapy of Aspergillus fumigatus keratitis. On day 15 after, the topical and combine classes had statistically significant better effect compared to the oral groups, but no distinguished difference was observed between topical and combine groups, suggesting that topical itraconazole were effective in lessening the severity of fungal keratitis in a rabbit model and systemic administration is not necessary.
方法:32只新西南大耳白兔刮去右眼角膜中央部上皮,接种烟曲霉菌孢子液于角膜表面,盖亲水性角膜接触镜,48小时后移去。造模成功后随机分为4组。点眼组:自制1%伊曲康唑混悬滴眼液点眼8次/d,每两小时一次;灌胃组:灌胃伊曲康唑胶囊40mg/kg/bid;联合组:点眼同时联合灌胃治疗剂量同前两组;对照组:生理盐水点眼8次/d,每两小时一次。裂隙灯显微镜照相记录观察成模后1, 3, 6, 10, 15, 20, 25d临床病理过程,分别记录临床评分,并发症发生率等。于成模后3, 6, 15, 25d分别行角膜菌丝刮片、真菌培养。于25d全部处死实验兔取角膜组织行病理学检查。
结果:1.比较各组间临床病理过程发现,4组病变早期表现基本一致,治疗第6d后3治疗组在各时间点从病理改变严重程度上较对照组有明显的减轻,病程长度也叫对照组有明显的缩短,治疗低15d后,点眼组、联合组的临床病理表现均较灌胃组轻,但点眼组与联合组之间没无明显差异。
2.治疗第1, 3d,各组临床评分比较无统计学差异,治疗第6d后,3治疗组临床评分均低于对照组且有统计学差异(P<0.01, Tukey HSD test),治疗第15d后,点眼组和联合组临床评分均低于灌胃组且差异有显著性(P <0.05, Tukey HSD test),但点眼组与联合治疗组比较则无显著差异(P>0.05, Tukey HSD test)。
3. 3治疗组前房积脓、角膜穿孔、角膜新生血管化等并发症发生率明显低于对照组且差异有显著性(P<0.01, Fisher’s exact test)。角膜组织刮片真菌阳性培养率在治疗后第6d明显低于对照组且差异有显著性(P<0.05, Fisher’s exact test),但第15, 25d真菌培养均为阴性。结论:1.我们所采用的改良角膜接触镜法对于实验性曲霉菌性角膜炎模型的制备有很高的成功率,本法可以用于曲霉菌性角膜炎模型的制备。
2.从本试验结果来看,局部和全身以及联合应用伊曲康唑对于实验性烟曲霉菌性角膜炎有良好的疗效。点眼组、联合组在治疗后期效果均优于灌胃组,但点眼组与联合组间没有明显差异,提示曲霉菌性角膜炎的治疗应以局部用药为主,全身用药并非必须。
Objective: To investigate the therapeutic role of topical, oral and combine itraconazole treatment using a rabbit model of Aspergillus fumigatus keratitis.
Methods: The epithelium was removed from the central cornea and a inoculum of Aspergillus fumigatus blastoconidia was placed on the corneal surface and covered with a soft contact lens. Forty-eight hours later, the thirty-two rabbits were randomly divided into four groups. Topical group eight rabbits were treated with topical itraconazole (1%, eight times daily), oral group eight rabbits received oral itraconazole (40mg/kg/bid), combine group eight rabbits were treated both topical itraconazole (1%, eight times daily) and oral itraconazole (40mg/kg/bid), untreated controls eight rabbits. The eyes were examined and photographed with a slit-lamp 1, 3, 6, 10, 15, 20 and 25 days after inoculation and an observer graded the corneas in a masked fashion. Corneal scraping, cultures were taken on days 3, 6, 15 and 25 for fungus growth.
Results: 1. Comparing the process of clinical pathology found that four groups consistent performance on 1 to 3 days. In the treated 6 day after, the three treatment groups in various points had significant lower the pathological changes and the course period than the control group. After day 15, the topical and combine groups had significant lower than oral groups, but no difference between topical and combine groups.
2. At the beginning of treatment, 1 to 3 days, the slit-lamp scores did not differ among four groups. However, after days 6 the three treated groups had statistically significant lower scores compared to the untreated controls (P<0.01). On day 15 the topical and combine classes had statistically significant lower marks compared to the oral groups (P<0.05), but no distinguished difference was observed between topical and combine groups at any examination point.
3. Three treated groups, complications such as hypopyon, corneal perforation and corneal neovascularization rate was significantly lower than the control group and there was a significant difference (P<0.01). On day 6, there were significantly lower positive fungal cultures in three treatment groups compared to the control (P<0.05). However, all cultures were negative on days 15-25.
Conclusions: 1. We improved the method of experimental fungal keratitis model which has a high rate of success used by soft contact lens, the method can be used for the model of fungal keratitis.
2. Our study showed that topical, oral and combine itraconazole were effective in lessening the severity of fungal keratitis in a rabbit model and should be considered effective treatment alternatives in the therapy of Aspergillus fumigatus keratitis. On day 15 after, the topical and combine classes had statistically significant better effect compared to the oral groups, but no distinguished difference was observed between topical and combine groups, suggesting that topical itraconazole were effective in lessening the severity of fungal keratitis in a rabbit model and systemic administration is not necessary.
引文
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