糖皮质激素激动剂Mapracorat对兔干眼症的疗效观察

Effect of Mapracorat on dry eye on rabbit models

目的:探讨糖皮质激素激动剂Mapracorat对兔蒸发过强型干眼症的疗效及兔泪液中白介素-6(IL-6)、肿瘤坏死因子-a(TNF-a)的影响。方法:健康成年雌性新西兰白兔(16只/组),经灼烧封闭睑板腺开口建立蒸发过强型干眼症模型,并经6周观察确认模型建立成功后随机分为两组:0.1%地塞米松(0.1%DEX)治疗组和0.5%Mapracorat治疗组,分别给予0.1%地塞米松磷酸钠溶液滴眼(1滴/次,3次/d),0.5%Mapracorat溶液滴眼(1滴/次,3次/d)。给药后分别在1、3、5周时间点进行裂隙灯下观察两组兔角膜形态,并进行Schirmer I实验、BUT时间测定、角膜荧光素染色评分,同时采集兔泪液进行IL-6、TNF-a的ELISA检测。结果:两组实验兔的蒸发过强型干眼症模型均建立成功,在模型第6周Schirmer I实验棉条湿润长度<10mm/5min,BUT时间<10s,角膜荧光素染色评分明显增加。0.5%Mapracorat治疗组与0.1%地塞米松治疗组比较,自给予开始后1、3、5周检测均表现出显著性优势,能明显增加Schirmer I实验棉条湿润长度,延长BUT时间,降低角膜荧光素染色评分(P<0.05)。泪液中IL-6、TNF-a含量在干眼症模型中明显高于正常基线水平,0.1%地塞米松和0.5%Mapracorat均能有效降低泪液中IL-1、TNF-a含量,且0.5%Mapracorat表现出更强的降低效果(P<0.05)。结论:Mapracorat可明显减轻蒸发过强型兔干眼症状,其机制可能与抑制眼表的炎性因子IL-6和TNF-a表达从而减轻炎症反应有关。

Objective： To investigate the therapeutic effect of Mapracorat on experimental evaporative rabbit dry eye model and on the alterations of IL-6, TNF-α in tears. Methods： Health female adult New Zealand White rabbits （16/group） were included and the Meibomian gland orifices were individually closed cauterization, and the dry eye models were established after 6 weeks observation. The rabbits with dry eye were randomly allocated into 2 groups： 0. 1% Dexamethasone treated group and 0.5% Mapracorat treated group. Schirmer I test, break-up time of cornea and fluorescent staining score were determined before and after drug intervention. The alterations of IL-6 and TNF-α in tear of dry eye were analyzed by ELISA assay. Results.. Compared with normal rabbits, the alterations of Schirmer I test, BUTT and Fluorescence stain of cornea could provide evidence to the successful model of dry eye. Compared to 0.1% Dexamethasone treated rabbits, rabbits with 0.5% Mapracorat showed the significant changes, such as the longer infiltrating sliver in Schirmer I test, the delayed BUT time and de creased scores of cornea fluorescence stain （P〈0.05）. The concentrations of IL-1 and TNF-α in tear fluid of rabbits with dry eye were determined by ELISA assay, and 0.5% Mapracorat treatment showed more efficacy than 0.1% Dexamethasone treat- ment on reduction of IL-1 and TNF-α in tear fluid （P〈0.05）. Conclusion： Mapracorat eye drop has a potential therapeutic effect on rabbit dry eye, the mechanism of which may be associated with the inhibition of the expression of inflammatory cyto- kines in ocular surface and the reduction of inflammatory response.