双氯芬酸钠对小鼠真菌性角膜炎抗真菌疗效的影响

发布时间：2018-03-09 21:59

本文选题：真菌性角膜炎　切入点：双氯芬酸钠　出处：《眼科新进展》2014年07期 　论文类型：期刊论文

【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P0.01);双氯芬酸钠组5 d与模型组相比,临床评分显著增加(P0.01);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P0.01)。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P0.05)。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P0.01);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P0.05);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P0.01)。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度,反而增加了真菌性角膜炎的临床评分,增加了角膜炎症细胞浸润,炎症细胞以中性粒细胞为主。提示进行真菌性角膜炎治疗时,慎用双氯芬酸钠。
[Abstract]:Objective to observe the therapeutic effect of antifungal drugs combined with diclofenac sodium on fungal keratitis. Methods C57BL / 6J mice were selected as experimental animals. The model of Fusarium vulgaris keratitis was used. The experiment was divided into 4 groups: operation control group (without mycelium inoculation, model group, model group). Ketoconazole group (ketoconazole alone) and diclofenac sodium group (ketoconazole combined with diclofenac sodium) were treated with slit-lamp and confocal microscopy respectively on the 1st day, 2nd day, 3d, 3d and 5d, respectively. The severity of keratopathy was evaluated under the lamp. The mycelium quantity and inflammatory cell count were measured with confocal microscope images in vivo. The corneal HE staining was performed 5 days after operation in the operation control group and diclofenac sodium group. The corneal clinical scores in ketoconazole group and diclofenac sodium group were significantly higher than those in the operation control group (P 0.01), and in diclofenac sodium group 5 days compared with the model group. Compared with ketoconazole group, the clinical score of diclofenac sodium was significantly higher than that of ketoconazole group at 4 and 5 days (P 0.01). The mycelium disappeared after 3 days in model group, ketoconazole group and diclofenac sodium group. Compared with the model group and ketoconazole group, the corneal mycelium area of diclofenac sodium group had no significant change (P 0.05). The model group, ketoconazole group and diclofenac sodium group were compared with the operation control group. At each time point, the number of inflammatory cells in cornea increased significantly (all P 0.01); the number of inflammatory cells in ketoconazole group was not significantly different from that in model group (all P 0.05); the number of inflammatory cells in diclofenac sodium group was higher than that in model group and ketoconazole group, and there was no significant difference between ketoconazole group and ketoconazole group. The number of inflammatory cells increased significantly in 4-5 days (all P 0.01). Pearson correlation analysis of inflammatory cell infiltration and clinical score of cornea in diclofenac sodium group showed that the number of inflammatory cells in the cornea was significantly higher than that in the control group (P < 0.05). The results of HE pathological examination in the operation control group and diclofenac sodium group showed that the corneal stromal cells in the operation control group were very few, the stromal cells in the diclofenac sodium group were thicker, and the stromal cells in the diclofenac sodium group were more than that in the diclofenac sodium group. The classified count of cells in the matrix showed that the confirmed neutrophils accounted for 72.67% of the total number of stromal cells. Conclusion the antifungal drugs were used in mice with fungal keratitis and diclofenac sodium was used locally. Not only can the severity of keratopathy not be alleviated, but the clinical score of fungal keratitis is increased, and the infiltration of inflammatory cells in the cornea is increased. The inflammatory cells are mainly neutrophil. It is suggested that in the treatment of fungal keratitis, Use diclofenac sodium with caution.
【作者单位】：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;
【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)~~
【分类号】：R772.21

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