基础医学与临床 ›› 2011, Vol. 31 ›› Issue (12): 1351-1357.

• 研究论文 • 上一篇    下一篇

三氧化二砷对实验性自身免疫性葡萄膜炎疗效的初步观察

强孚勇1,2,嘉婷2,张挺2,孙莉2,朱小春2   

  1. 1. 个体住户
    2. 温州医学院附属第一医院
  • 收稿日期:2010-09-06 修回日期:2011-05-20 出版日期:2011-12-05 发布日期:2011-12-05
  • 通讯作者: 朱小春 E-mail:zhuxiaochunwz@yahoo.com.cn
  • 基金资助:
    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)

The Observation of Primary Therapeutic Effect of Arsenic Trioxide Treated Experimental Autoimmune Uveitis

  • Received:2010-09-06 Revised:2011-05-20 Online:2011-12-05 Published:2011-12-05

摘要: 目的 初步探讨三氧化二砷(arsenic trioxide ,ATO)对实验性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(interphotoreceptor retinoid-binding protein ,IRBP)R14多肽免疫雌性Lewis大鼠后随机分为ATO高剂量组、ATO中剂量组、ATO低剂量组、环孢素A(CsA)组和生理盐水组5组,每组5只,分别腹腔注射ATO 5mg/(kg•d)、ATO 2mg/(kg•d)、ATO 0.5mg/(kg•d)、CsA 2mg/(kg•d)及生理盐水2ml/(kg•d)。裂隙灯显微镜观察大鼠眼前房炎症情况,第15天时处死大鼠,光学显微镜观察大鼠眼球的病理变化程度,实验前后记录各组大鼠体重变化情况,免疫组织化学方法观察大鼠眼球中T-bet+Th1及FOXP3+调节性T细胞的浸润情况。结果 生理盐水组和ATO 0.5mg/(kg•d)组可见明显的虹膜充血、血管扩张和脓性渗出,ATO 5mg/(kg•d)组和CsA组前房炎症反应程度较轻。ATO 2mg/(kg•d)组眼部炎症表现比较明显。与生理盐水组比较,ATO 5mg/(kg•d)组、ATO 2mg/(kg•d)组和CsA组的临床评分均有所降低,差异均有统计学意义(P =0.000、P =0.004及P =0.008),ATO 5mg/(kg•d)组比ATO 2mg/(kg•d)组的临床评分要低(P =0.046)。组织病理学评分显示各组间差异有统计学意义(F=31.75,P =0.000)。与生理盐水组比较,CsA组、ATO 5mg/(kg•d)组和ATO 2mg/(kg•d)组差异均有统计学意义(P =0.000、P =0.000和P =0.000)。ATO 5 mg/(kg•d)组比ATO 2 mg/(kg•d)组的病理评分低(P =0.000)。与正常大鼠相比,各组大鼠在实验前后体重改变无明显差异(P >0.05)。与生理盐水组比较,ATO 5mg/(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 ATO 5mg/(kg•d)腹腔内注射治疗EAU大鼠能明显改善其前房充血、渗出等炎症表现,改善其视网膜病理变化,减少Th1细胞在眼内的渗出来抑制眼内炎症反应,对眼内的FOXP3+调节性T细胞无明显影响,且对大鼠的生长无明显的抑制作用。

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

Abstract: Objective This study is to investigate the therapeutic effect and mechanism of ATO treated EAU in rats. Methods EAU models were induced in 25 SPF female Lewis rats aged 6 weeks 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)、2mg/(kg•d) or 0.5mg/(kg•d) respectively for 15 days in 5 model rats,and 2 mg/(kg•d) 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 slitlamp biomicroscopy every day and histological score of retinas was evaluated on day 15 after immunization. Weight of rats of all groups were recorded before and after experiment. The infiltration of T-bet+Th1 cells and FOXP3+Treg cells was detected by immunochemistry. Results The congestion of iris vessels,fibrous exudates and retroiridal hypopyon were found in the rats of ATO 0.5mg/(kg•d) group and normal saline solution.However,mild inflammatory response at ocular anterior segment was seen in the rats from CsA group and ATO 5mg/(kg•d) group under the slim lamp.The obvious congestion of iris vessel,fibrous exudates and mild retroiridal hypopyon are found in the rat of ATO2mg/(kg•d) . The clinical score was significantly lower in ATO 5mg/(kg•d) 、ATO 2mg/(kg•d) and CsA group compared with normal saline solution group(P =0.000、P =0.004 and P =0.008), The clinical score was significantly lower in ATO 5mg/(kg•d) compared with ATO 2mg/(kg•d)(P =0.046). The retinal histopathological score showed significant difference among CsA group、ATO 5mg/(kg•d)、ATO 2mg/(kg•d) group and normal saline solution group(F=31.75,P =0.000) . The histopathological score was significantly lower in CsA group、ATO 5mg/(kg•d) and ATO 2mg/(kg•d) group compared with normal saline solution group(P =0.000、P =0.000 and P =0.000).There were no significant difference among the weight of all groups after experiment( P >0.05). The exudation of T-bet+Th1 cells was apparently decreased in 5mg ATO group,2mg ATO group and CsA group in comparison with normal saline solution group,and the numbers of FOXP3+Treg cells in retina were similar in all groups. Conclusion Intraperitoneal injection of ATO 5mg/(kg•d) is effective in suppressing the ongoing process of EAU by inhibiting infiltration of T-bet+Th1

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