中文摘要：

目的探讨米诺环素滴眼液对苯扎氯铵诱导的小鼠干眼的疗效及可能机制。方法 BALB/c雄性小鼠50只（100眼）使用0.2%的苯扎氯铵滴眼液滴眼诱导干眼。选择严重程度相似的干眼小鼠随机分为A、B、C、D 4组,分别为0.1%米诺环素滴眼液组、0.5%米诺环素滴眼液组、溶剂组及空白组。在治疗前及治疗后第1、3及5天,行泪膜破裂时间（BUT）、角膜炎症指数、角膜上皮荧光素钠染色检查。治疗结束后摘取小鼠眼球,行HE及过碘酸-希夫染色（PAS）,免疫组织化学及免疫荧光检测角膜组织角蛋白10（K10）的表达,Western blot检测角组织中白细胞介素-1β（IL-1β）及肿瘤坏死因子-α（TNF-α）的表达水平,并分析各组的差异。结果共40只小鼠（80眼）入选进行治疗实验,每组10只（20眼）。用药前各组小鼠BUT、角膜炎症指数、角膜上皮荧光素钠染色差异无统计学意义（F=0.19、0.24和0.81;P=0.902、0.869和0.493）。用药后第3天及第5天,A、B组较C、D组角膜炎症程度明显减轻（F=6.57及10.17;P=0.001和0.000）,泪膜破裂时间延长（F=5.71及5.36;P=0.003及0.004）。治疗第3天,A、B组较C、D组角膜荧光素钠染色轻（F=4.42,P=0.009）。HE染色结果显示A、B组角膜上皮细胞形态较C、D组规整。PAS染色显示A、B组杯状细胞数量多于C、D组（F=15.36,P=0.007）。免疫组织化学及免疫荧光结果均显示A、B组较C、D组K10表达减少（F=162.50,P=0.000）。Western blot显示A、B组较C、D组IL-1β、TNF-α表达明显降低（F=6.84及11.60;P=0.006及0.001）。结论米诺环素对苯扎氯铵诱导的小鼠干眼有一定的治疗作用,其机制可能与其抑制眼表炎症及鳞状上皮化生有关。

英文摘要：

【Objective】To investigate the effects of minocycline eye drops on dry eye in a mouse model induced by topical benzalkonium chloride（BAC） and outline the mechanism.【Methods】Fifty male BALB/c mice were treated with topical administration of 0.2% BAC to induce dry eye. According to clinical evaluations including tear break-up time（BUT）, corneal fluorescein staining scores and inflammation index on day（D） 15 after the BAC treatment, the similar severity dry eye mice（80 eyes）were selected and randomly divided into four groups： A（0.1%minocycline-treated group）, B（0.5% minocycline-treated group）, C（solvent-treated group）, and D（blank group）.Clinical evaluations including BUT, corneal fluorescein staining, and inflammatory index were performed on D1, D3 and D5 after treatment. Eyeballs were collected on D5 and evaluated by histologic investigation, immunostaining using antibodies against cytokeratin 10 in the cornea was performed, and goblet cells were detected by the periodic acid-Schiff（PAS） assay. The levels of IL-1β, TNF-α were measured by Western blot. 【Results】Eighty eyes were included in the sequential experiment, 20 eyes for each group. There were no clinical differences among the groups before the treatment. Lower inflammatory index scores and longer BUT were recorded on D3 and D5 in minocyclinetreated eyes, and lower corneal fluorescein staining scores were recorded on D3 in minocycline-treated eyes. The expression of cytokeratin 10 was reduced in minocycline-treated eyes. The expressions of IL-1β, TNF-α were inhabited in minocycline-treated eyes. In addition, minocycline relatively increased the number of goblet cells.【Conclusion】Topical minocycline application produced improvements in dry eye, most likely by inhibiting inflammation and squamous metaplasia.