强力霉素对大鼠干眼症的疗效观察及眼角膜组织中IL-6和TNF-α的表达变化

摘要

目的 探讨强力霉素对大鼠干眼症的疗效及眼角膜组织中IL-6、TNF-α的表达变化.方法 健康成年SD大鼠48只,摘除主泪腺后建立中重度干眼大鼠模型,随机分为3组进行药物干预,每组16只大鼠,16只眼,分别为:强力霉索组(doxy组),1g/L强力霉素溶液滴眼,4次/d；羧甲基纤维素组(CMC组),10 g/L羧甲基纤维素滴眼,4次/d; NaCl组为生理盐水滴眼,4次/d.给药后1、2、5周分别在裂隙灯下观察各组大鼠角膜形态并进行Schirmer Ⅰ实验、BUT时间( break-up time)测定、荧光素染色评分,5周后应用免疫组化方法检测角膜组织中的IL-6和TNF-α的表达.结果 与NaCl组比较,治疗5周时doxy组大鼠角结膜表面湿润度明显增加,Schirmer Ⅰ试验滤纸湿长(9.56±0.94)mm/5 min,BUT时间(9.53±1.06)s,荧光素染色评分(3.37±2.94)分,有显著性差异(P＜0.05).IL-6和TNF-α在3组大鼠角膜中均见表达,doxy组角膜组织中1 000个细胞的IL-6和TNF-α阳性细胞数分别为:78.67±25.29、55.18±28.93,较同一时间CMC组及NaCl组IL-6和TNF-α阳性表达的细胞数明显减少,差异有统计学意义(P＜0.05).结论 强力霉素滴眼液可明显减轻大鼠干眼症状,其机制可能与抑制眼表的炎性因子IL-6和TNF-α表达从而减轻炎症反应有关.%Objective To observe the therapeutic effect of doxycyline on tear deficiency dry eye in rats and the expressions of IL-6 and TNF-a as anti-inflammatory mediators in dry eye. Methods Forty-eight adult healthy SD rats with main lacrimal gland removed were selected as the model of dry eye. These rats were equally divided into 3 groups. 1 g/L doxycycline eye drops group, 10 g/L carboxymethyl cellulose eye drops group and normal saline eye drops group, administered with eye drops four times daily respectively. 1,2,5 weeks after drug administration, corneal shape, Schirmer I experiment (Sit), break-up time (BUT) and fluorescent staining score were observed under slit lamp. Expressions of corneal epithelial IL-6 and TNF-a were detected by immunohistochemistry. Results Compared with those in saline group at fifth week, corneal surface moisture degree increased in doxy group rats, Sit filter paper wet long was (9. 56 +0.94)mm/5 min, BUT was (9. 53± 1. 06)s, and fluorescence staining score was 3.37±2. 94 (P＜0.05). In doxycycline group, IL-6 and TNF-a positive cell counts were (78.67± 25. 29)/l 000 cells and (5.18±28.93)/l 000 cells; the number of cells with positive IL-6 and TNF-a expressions was significantly reduced (P＜0.05) compared with that in carboxy methyl cellulose group and the saline group at the same time point. Conclusion Doxycycline eye drop has an obvious therapeutic effect on rat dry eye, which may be related to its lessening inflammatory reaction by inhibiting the expressions of inflammatory factors IL-6 and TNF-a of rat eye surface.