GABA受体激动剂在干眼模型中对炎症反应的调节作用及对眼表修复的影响

Anti-Inflammatory and Promoting Ocular Surface Effects of GABAAR Agonists in DED Mice

摘要: 目的：观察GABA A型受体激动剂Muscimol对干眼模型鼠眼中TNF-α、IL-1β表达的调节作用及对眼表修复的影响。方法：选用SPF级雌性C57BL/6小鼠(7~8周龄)，用3 mg/mL东莨菪碱溶液皮下注射，同时模拟干燥环境建立干眼症模型，14天后给予3 mg/mL Muscimol溶液结膜下注射。于1、3、5天行泪液分泌量测定及荧光素钠染色，同时制备眼表组织切片，采用苏木素–伊红染色法评估角膜组织形态学变化。分别采用PCR、ELISA方法检测小鼠结膜组织中TNF-α和IL-1β的mRNA及蛋白的表达。结果：在使用Muscimol处理后的第1、3天各项临床指标均有恢复趋势，第5天后的泪液分泌量显著增加(P < 0.01)，角膜荧光素钠染色分级减轻(P < 0.01)。角膜组织切片的HE染色结果显示，Muscimol处理组角膜上皮规整，相应损伤有所减轻。Muscimol处理组TNF-α和IL-1β的mRNA及蛋白的表达均呈下降趋势，第5天差别具有统计学意义(均P < 0.01)。结论：Muscimol结膜下注射可抑制干眼模型小鼠结膜中炎症因子的表达，促进眼表损伤的修复。

Abstract: Objective: To investigate the regulation of GABA type A receptor agonist Muscimol to the expres-sions of TNF-α and IL-1β and the effect on ocular surface repair in mice dry eye models. Methods: Female C57BL/6mice (7~8 weeks) were injected subcutaneously with scopolamine solution (3 mg/mL) in a dry environment. After 14 days, the mice were injected subconjunctivally with Musci-mol solution (3 mg/mL). Tear secretion, fluorescein staining score, and HE staining were examined on the 1st, 3rd, 5th day. PCR and ELISA quantified the mRNA and protein expressions of TNF-α and IL-1β. Results: All the clinical indexes demonstrated a recovery trend after Muscimol treatment. Tear secretion increased significantly (P < 0.01), and fluorescein staining score decreased (P < 0.01) on the 5th day. HE staining showed that the corneal epithelium damage had repaired in the Musci-mol treated group. The mRNA and protein expressions of TNF-α and IL-1β in the Muscimol treated group decreased significantly (P < 0.01 for all) on the 5th day. Conclusion: The application of Mus-cimol can inhibit the expression of inflammatory factors in the conjunctiva of dry eye model mice, and promote the repair of ocular surface.