Objective To investigate the therapeutic effect and mechanism of ATO used in EAU treatment. Methods < EAU models were developed in 25 female Lewis rats by the injection of interphotoreceptor retinoid-binding protein (IRBP) to planta and ATO was administrated by intraperitoneal injection at a does of 5 mg/(kg · d) , 2 mg/(kg · d) or 0. 5 mg/(kg · d) respectively for 15 days, and 2 mg/(kg · d) of cyclosporine A( CsA) was used in the same way in CsA group, and normal saline solution was injected as positive control group. EAU was assessed under the slit-lamp biornicroscopy every day and histological score of retinas was evaluated on day 15 after immunization. Quality of rats of all groups were recorded before and after experiment. The infi-ltration of T-bet + Thl cells and F0XP3 +Treg cells was detected by immunochemistry. Results Obvious inflammatory response was found in the rats of ATO 0. 5 mg/(kg · d) group and normal saline solution. However,mild inflammatory response at ocular anterior segment was seen in CsA group and ATO 5 mg/( kg ? d) group. The clinical score was significantly lower in ATO 5 mg/(kg ? d) , ATO 2 mg/(kg · d) and CsA group compared with normal saline solution group (P < 0.05 ). The retinal histopathological score showed significant difference among CsA group, ATO 5 mg/(kg · d) , ATO 2 mg/(kg · d) group and normal saline solution group (P < 0. 05 ). The histopathological score was significantly lower in CsA group, ATO 5 mg/(kg · d) and ATO 2 mg/(kg · d) group compared with normal saline solution group(P <0. 05). The exudation of T-bet + Thl cells was decreased in 5 mg ATO group, 2 mg ATO group and CsA group in comparison with saline solution group, and the numbers of FOXP3 + Treg cells in retina were similar in all groups. Conclusions Intraperitoneal injection of ATO 5 mg/( kg ? d) is effective in suppressing the ongoing process of EAU by inhibiting infiltration of T-bet + Thl cells.%目的 探讨三氧化二砷(ATO)对自身免疫性葡萄膜炎(EAU)大鼠模型的疗效及机制.方法 用光感受器间维生素A类结合蛋白(IRBP)R14多肽免疫雌性Lewis大鼠后,随机分为ATO 5 mg/kg、2 mg/kg、0.5 mg/kg、环孢素A (CsA)2 mg/kg和对照组0.9％氯化钠注射液2mL/kg 5组,每组5只,分别每日腹腔注射.裂隙灯显微镜观察大鼠眼前房炎性反应,第15天时观察大鼠眼球的病理改变及质量变化,免疫组化观察大鼠眼球中T-bet+ Th1及FOXP3+调节性T细胞浸润情况.结果 0.9％氯化钠注射液组和ATO 0.5 mg/(kg·d)组可见明显的前房炎性反应,ATO 5 mg/(kg·d)组和CsA组炎性反应较轻.CsA组、ATO 5 mg/( kg·d)组和ATO2 mg/(kg·d)组的临床评分均显著低于0.9％氯化钠注射液组(P＜0 05).病理评分显示各组间有显著差异(P＜0.05).CsA组、ATO5 mg/(kg·d)组和ATO 2 mg/( kg·d)组病理评分均显著低于0.9％氯化钠注射液组(P＜0 05).与0 9％氯化钠注射液组比较,ATO 5 mg/(kg·d)组和CsA组的T-bet+ Th1细胞浸润明显减少.FOXP3+调节性T细胞在各组间并无明显差别.结论 腹腔注射ATO 5 mg/(kg·d)可以减少Th1细胞在眼内的浸润来抑制大鼠EAU.
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