雷帕霉素缓释微球治疗干燥综合征性干眼的疗效评估

Effect assessment of subconjunctival injection of rapamycin-loaded microspheres in non-obese diabetic mice with dry eye caused by Sjgren's syndrome

目的:观察结膜下注射新型免疫抑制剂雷帕霉素缓释微球对NOD小鼠干燥综合征(Sjgren's syndrome,SS)性干眼临床体征的改善。方法:SS性干眼的8周龄雌性NOD模型小鼠20只,随机分为4组,每组5只,9周龄时开始给药。另有5只8周龄健康KM小鼠作为正常对照组。实验Ⅰ组和Ⅱ组小鼠分别给予200μg/kg和400μg/kg的雷帕霉素缓释微球结膜下注射,实验Ⅲ组和Ⅳ组动物分别给予生理盐水和空白微球载体结膜下注射。用药前及用药后第5,10,15,20d检查各组小鼠的泪液分泌量,对角膜行荧光素染色并评分,对角结膜行虎红染色并评分,用结膜印记细胞学方法检测结膜细胞并分级。结果:实验组与对照组相比,泪液分泌量明显增加,角膜荧光素染色和角结膜虎红染色评分降低,结膜印记细胞学等级降低。结论:雷帕霉素缓释微球可以通过抑制细胞免疫反应,增加NOD小鼠泪液分泌量,对NOD小鼠干燥综合征性干眼具有显著疗效。

AIM： To study the effect of rapamycinloaded microspheres in non-obese diabetic （NOD） mice with dry eye caused by SjSgren＇s syndrome（ SS）. METHODS： Twenty 8-week-old female NOD mice with dry eye caused by SS were randomly divided into 4 groups. One week later, the mice were treated with subconjunctival injection. Group I and II received 2001J g/kg and 400tJg/kg rapamycin-loaded microspheres, Group Ill and IV received normal saline and empty microspheres. Five 8-week-old female healthy KM mice were used as untreated controls. Before and 5, 10, 15, 20 days after the experiment, the amount of secretion of tears, the score of corneal fluorescein staining and rose bengal staining were investigated. Conjunctival epithelial cells were observed and graded by conjunctival impression cytology. RESULTS： Compared with the group III and IV, the amount of secretion of tears of the mice in group I and II increased. The scores of corneal fluorescein staining androse bengal staining were lower. The levels of conjunctival impression cytology reduced. CONCLUSION： Rapamycinloaded microspheres can decrease dry eye signs by alleviating the ocular surface inflammation of NOD mice. It suggests rapamycin-loaded microsphere is valuable to dry eye caused by SS.