三氧化二砷对大鼠自身免疫性葡萄膜炎疗效的初步观察  

The therapeutic effect of arsenic trioxide on experimental autoimmune uveitis in rats

作　　者：强孚勇[1] 嘉婷[1] 张挺[1] 孙莉[1] 朱小春[1] 

机构地区：[1]温州医学院附属第一医院风湿免疫科,浙江温州325000

出　　处：《基础医学与临床》2011年第12期1351-1357,共7页Basic and Clinical Medicine

基　　金：浙江省眼科学-视觉科学医学重点学科群基金(437210702);温州市科技局科技计划项目(Y20090240)

摘　　要：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ATO 2 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。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 as- sessed under the slit-lamp biomicroscopy 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 FOXP3 ＋ 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 significant- ly lower in ATO 5 mg/（ kg · d）, ATO 2 rag/（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 sup- pressing the ongoing process of EAU by inhibiting infiltration of T-bet ＋ Th1 cells.

关 键 词：实验性自身免疫性葡萄膜炎 三氧化二砷 光感受器间维生素A类结合蛋白 免疫组织化学 

分 类 号：R773.9[医药卫生—眼科] R988.1[医药卫生—临床医学]