细胞因子信号传导抑制因子在实验性自身免疫性葡萄膜视网膜炎视网膜内的表达  

Expression of suppressor of cytokine signaling in retina of experimental autoimmune uveoretinitis

作　　者：王红[1] 周增超[1] 彭晓燕[1] 赵萌[1] 

机构地区：[1]首都医科大学附属北京同仁医院北京同仁眼科中心,100730

出　　处：《中华眼科杂志》2008年第10期876-882,共7页Chinese Journal of Ophthalmology

基　　金：国家自然科学基金资助项目（30400490）;北京市自然科学基金资助项目（7052023）;北京市科技新星计划（A）类资助项目（2003A23）

摘　　要：目的探讨细胞因子信号传导抑制因子（SOCS）在实验性自身免疫性葡萄膜视网膜炎（EAU）视网膜内的表达与意义。方法随机对照实验设计方法。90只Lewis大鼠采用分层随机抽样进行分组，分别为未治疗组40只大鼠、治疗组40只大鼠及正常对照组10只大鼠。用光感受器间维生素A类结合蛋白（IRBP）诱导EAU动物模型，治疗组从免疫后1—28d，给予环孢素（CsA）灌胃，每天20mg／kg体重，而未治疗组给予等量生理盐水，正常对照组未给予免疫和治疗。分别于免疫后7、14、21、28d按分层随机号抽取治疗组与未治疗组各10只大鼠进行相关检测，观察大鼠眼部炎性变化，双眼取材，分别用实时荧光定量聚合酶链反应和蛋白免疫印迹法检测大鼠视网膜内SOCSmRNA和蛋白的表达，酶联免疫吸附试验方法检测血清细胞因子白细胞介素4（IL4）、IL-12、干扰素1（IFN-γ）的水平。利用单因素方差分析对治疗组与未治疗组大鼠血清中细胞因子的浓度和视网膜内SOCS蛋白表达量进行对比分析，多重比较采用最小显著差异法；用Mann—Whitney两样本比较秩和检验进行治疗组与未治疗组大鼠炎性反应分值比较。结果免疫后14d，未治疗组可见明显的虹膜睫状体炎，房水闪辉阳性，虹膜后粘连，瞳孔不规则甚至前房积脓，炎性反应分值是1．5±0．5；而治疗组眼部炎性反应不明显，炎性反应分值是0．5±0．3。未治疗组的IL-12、IFN-γ及IL-4免疫后14d达到最高峰（均P〈0．05），免疫后28dIL-12、IFN-γ下降到正常水平（均P〉0．05），IL-4仍高于正常对照组（P〈0．05）；治疗组中IL-12、IFN-γ的动态变化不明显（均P〉0．05），IL-4在整个病程中呈上升趋势（均P〈0．05）。SOCS1、含SH2结构的细胞因子诱导蛋白（CIS）mRNA免疫后14d表达最高，未治疗组分别是正常对照组的3．41倍和3．36倍，治疗组分别为1．44Objective To investigate the expression and significance of suppressor of cytokine signaling （SOCS） mRNA and protein in retina of rats with experimental autoimmune uveoretinitis （EAU）. Methods Research was designed with randomized controlled trials. Eighty Lewis rats were immunized with interphotoreceptor retinoid-binding protein （IRBP） to induce EAU. They were stratified randomly into two groups ： nontreatment group （40 rats） and treatment group （ 40 rats ）. The treatment group was administered cyclosporine A 20 mg · kg^-1· day^-1 after immunization for 28 days, and the nontreatment group received saline buffer in the same way, ten normal Lewis rats without immunization and treatment as normal control group. The rats in both groups were stratified randomly into four sub-groups. Each sub-group had 10 rats and the rats were sacrificed at day 0, 7, 14, 21, 28 after immunization. All eyes were evaluated by slit-lamp microscopy. Retinas of rats were subjected to analysis of SOCS mRNA and protein expression using quantitative RT-PCR and western blot, respectively. IL-4,IL-12 and IFN-γ in the serum were measured by ELBA. Results At day 14, the nontreatment group developed acute anterior uveitis and showed typical signs including aqueous flare, small or irregular pupil due to posterior synechiae and hypopyon, the score of inflammation was 1.5 -0. 5; but the treatment group did not suffer from severe anterior chamber inflammation, the score of inflammation was 0. 5 ± 0. 3. The highest level of IL-4, IL-12 and IFN-γ production occurred at day 14 （P 〈 0. 05 ） , followed by decline in the secretion of IL-12 and IFN-γ secretion to the baseline at day 28, while the concentration of IL-4 did not decrease significantly in the nontreatment group（P 〉 0. 05 ）. IL-12 and IFN-γ did not change significantly （ P 〉 0. 05 ） and IL-4 production reached the highest level at day 28 in the treatment group. Both SOCS1 and CIS mRNA increased to the highest level at day 14. Compared to normal cont

关 键 词：自身免疫疾病 葡萄膜炎 视网膜炎 阻遏蛋白质类 胞间信号肽类和蛋白质类 

分 类 号：R686[医药卫生—骨科学]