三氧化二砷对实验性自身免疫性葡萄膜炎大鼠的治疗作用

目的探讨三氧化二砷（As2O3）对实验性自身免疫性葡萄膜炎（EAU）大鼠模型的治疗作用。方法将光感受器间维生素A类结合蛋白（IRBP）R14多肽免疫大鼠随机分为高剂量As2O3组、低剂量As2O3组、环孢素A（CsA）组和生理盐水组4组,每组5只,分别腹腔注射5 mg/kg As2O3、0.5 mg/kg As2O3、2 mg/kg CsA及生理盐水0.2 mL。裂隙灯显微镜观察大鼠眼前房炎症情况,第14天时处死大鼠,光学显微镜观察大鼠眼球的病理变化程度,免疫组织化学观察大鼠眼球中CD3＋T细胞的浸润情况,TUNEL法检测大鼠视网膜组织的凋亡。结果生理盐水组和0.5 mg/kg As2O3组可见明显的虹膜充血、血管扩张和脓性渗出,5 mg/kg As2O3组和CsA组前房炎症反应程度明显较轻,与生理盐水组比较,5 mg/kg As2O3组和CsA组的临床评分明显降低,差异均有统计学意义（tAs2O3 5 mg=-0.656,P=0.042;tCsA=-1.308,P=0.002）。组织病理学评分显示各组间差异有统计学意义（F=11.297,P=0.000）。与生理盐水组比较,As2O3组和CsA组的CD3＋T细胞浸润明显减少。TUNEL检测细胞凋亡在各组间差异无统计学意义（P〉0.05）。结论腹腔注射As2O3可以明显抑制EAU大鼠的临床表现、病理改变及CD3＋T细胞的浸润,未增加病变部位细胞的凋亡。

Treatment of experimental autoimmune uveitis in rats with arsenic trioxide

Background Uveitis is a refractory ocular disease with the causing-blindness rate 2.8%-10%,and its pathogenesis mechanism is less clear.Autoimmune uveitis（EAU） animal model is certified to be a good studying tool.Research showed that arsenic trioxide（As2O3） is a promising immunity inhibitor.ObjectiveThis study is to determine whether intraperitoneal injection of As2O3 suppresses ongoing experimental EAU in rats.MethodsEAU models were induced in 20 SPF female Lewis rats aged 6-8 weeks by the injection of interphotoreceptor retinoid-binding protein（IRBP） to planta and simultaneously intraperitoneal injection of pertussis toxin（PTX）.As2O3 was administrated by intraperitoneal injection at a does of 5mg/kg or 0.5mg/kg respectively for 14 days in 5 model rats,and 2 mg/kg of cyclosporine A（CsA） was used at the same way in CsA group,and normal saline solution was injected in 5 model rats as positive control group.EAU was assessed under the slit-lamp biomicroscopy every day,and histological score of retinas was evaluated on day 14 after immunization.The infiltration of CD3＋ cells was detected by immunochemistry and cellular apoptosis was detected by TUNEL assay.The use of animals followed the Standard of Association for Research in Vision and Ophthalmology.Results The congestion of iris vessels,fibrous exudates and retroiridal hypopyon were found in the rats of 0.5 mg As2O3 group and normal saline solution.However,mild inflammatory response at ocular anterior segment was seen in the rats from CsA group and 5 mg As2O3 group under the slim lamp.The clinical score was significantly lower in CsA group and 5mg As2O3group compared with normal saline solution group（tAs2O35mg=-0.656,P=0.042;tCsA=-1.308,P= 0.002）.The retinal histopathological score showed significant difference among CsA group,5mg As2O3 group and normal saline solution group（F=11.297,P=0.000）.The invasion of CD3＋ T cells was evidently decreased in 5mg As2O3 group,0.5mg As2O3 group and CsA group in comparison with normal saline solution group,and the numbers of apoptotic cells in retina were similar in As2O3 group and normal saline solution group.Conclusion Intraperitoneal injection of As2O3 is effective and safe in suppressing the ongoing process of EAU.