双氯芬酸钠对小鼠真菌性角膜炎抗真菌疗效的影响  

Influence of diclofenac sodium on therapeutic effects of antifungal drugs for fungal keratitis in mice

作　　者：张红敏[1] 刘素素[1] 李金[1] 柳慧[1] 谢艳亭[1] 王丽娅[1] 

机构地区：[1]河南省立眼科医院&河南省眼科研究所,河南省人民医院眼科,郑州大学人民医院眼科,河南省郑州市450003

出　　处：《眼科新进展》2014年第7期607-611,共5页Recent Advances in Ophthalmology

基　　金：国家自然科学基金项目(编号:81170831、81270991);河南省基础与前沿计划项目(编号102300410024、112300410036、11230040093、132102310087);河南省科技创新人才计划项目(编号144100510019)~~

摘　　要：目的观察抗真菌药物联合双氯芬酸钠对真菌性角膜炎的治疗效果。方法选取C57BL/6J小鼠为实验动物,以腐皮镰孢菌性角膜炎为模型。实验分为4组:手术对照组(不进行菌丝接种)、模型组、酮康唑组(单纯酮康唑治疗)和双氯芬酸钠组(酮康唑联合双氯芬酸钠治疗)。每组于造模后1 d、2 d、3 d、4 d和5 d分别进行裂隙灯观察和活体共焦显微镜检查。裂隙灯下进行角膜病变严重程度临床评分;对活体共焦显微镜图片进行菌丝定量和炎症细胞计数。手术对照组和双氯芬酸钠组于手术后5 d进行角膜HE染色病理学检查。结果模型组、酮康唑组和双氯芬酸钠组与手术对照组相比,各时间点角膜临床评分均有显著性增加(均为P<0.01);双氯芬酸钠组5 d与模型组相比,临床评分显著增加(P<0.01);双氯芬酸钠与酮康唑组相比,3 d、4 d和5 d的角膜临床评分显著增加(均为P<0.01)。模型组、酮康唑组和双氯芬酸钠组3 d后角膜内菌丝消失;双氯芬酸钠组与模型组和酮康唑组相比,角膜内菌丝面积无明显变化(均为P>0.05)。模型组、酮康唑组和双氯芬酸钠组与手术对照组相比,各时间点角膜炎症细胞数均有显著增多(均为P<0.01);酮康唑组与模型组比较,各时间点炎症细胞数无显著性差异(均为P>0.05);双氯芬酸钠组与模型组和酮康唑组相比,炎症细胞数目4-5 d均有显著性增多(均为P<0.01)。双氯芬酸钠组角膜内炎症细胞浸润与角膜临床评分的Pearson相关分析显示,二者呈明显正相关(r=0.860,P=0.000)。造模后5 d,手术对照组和双氯芬酸钠组HE病理学检查结果显示:手术对照组角膜基质内细胞很少;双氯芬酸钠组基质增厚,基质内细胞增多,基质内细胞分类计数显示,可以确认的中性粒细胞占基质所有细胞总数的72.67%。结论小鼠真菌性角膜炎进行抗真菌药物治疗的同时局部应用双氯芬酸钠,不但不能减轻角膜病变的严重程�Objective To observe the therapeutic effects of antifungal drugs combined with diclofenac sodium on corneal fungal keratitis. Methods C57BL/SJ mice were chosen as experimental animals and Fusarium solani fungal keratitis as a model. Experiment was divided into four groups： control group, fungal keratitis model group, ketoconazole treatment group （ ketoconazole therapy alone） and diclofenac sodium treatment group （treated with ketoconazole and diclofenac sodium）. Each group was examined with slit lamp microscope and in vivo confocal scanning microscope at 1 day,2 days,3 days,4 days and 5 days after operation. The severity of corneal disease was evaluated by clinical score with slit lamp microscope. The hypha areas and number of inflammatory cells in vivo confocal microscopy images were quantitated. The corneal pathological examination of control group and diclofenac sodium treatment groups were conducted with HE staining at postoperative 5 days. Results Clinical scores of cornea at each time point in fungal keratitis model group ,ketoconazole treatment group and diclofenac sodium treatment group were significantly higher than that in control group （P 〈0.01 ）. The clinical scores at postoperative 5 days in diclofenac sodium treatment group was significantly higher than that of model group （P 〈0.001 ）. The clinical scores at postoperative 3 days,4 days and 5 days in diclofenac sodium treatment group were significantly higher than those in ketoconazole treatment groups. The corneal hypha disappeared at postoperative 3 days in model groups and ketoconazole treatment groups. The area of corneal hypha had no significant change in diclofenac sodium treatment group compared with model group and ketoconazole treatment group （ P 〉 0.05 ）. The number of corneal inflammatory cells in fungal keratitis model group, ketoconazole treatment group and diclofenac sodium treatment group at each time point were significantly more than that in control group （P 〈0.01 ）. No significant differences in the

关 键 词：真菌性角膜炎 双氯芬酸钠 酮康唑 中性粒细胞 鼠 

分 类 号：R587.102[医药卫生—内分泌]