SOCS1反义寡核苷酸对实验性自身免疫性葡萄膜视网膜炎的作用  

Effect of SOCS1 antisense oligonucleotides on experimental autoimmune uveoretinitis

作　　者：周增超[1] 王红[1] 彭晓燕[1] 赵萌[1] 梁亮[1] 刘云霞[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,北京100730

出　　处：《眼科研究》2008年第9期653-657,共5页Chinese Ophthalmic Research

基　　金：国家自然科学基金(30400490);北京市自然科学基金(7052023)资助

摘　　要：目的探讨细胞因子信号抑制因子1(SOCS1)反义寡核苷酸对预防实验性自身免疫性葡萄膜视网膜炎(EAU)的可行性和有效性。方法制作大鼠EAU模型,于免疫后10d前房内分别注射SOCS1反义寡核苷酸脂质体(A组)、SOCS1正义寡核苷酸脂质体(B组)、脂质体(C组)和生理盐水(D组)。于14、21、28d观察其炎症反应,检测外周血单个核细胞(PBMC)、视网膜内SOCS1 mRNA及蛋白的表达和血清中IL-4、IL-12和IFN-γ的含量。结果免疫后14d、21d,B、C、D组可见明显的虹膜睫状体炎,A组炎症反应不明显;与D组相比,A组IL-4升高,IL-12和IFN-γ降低(P<0.05),B组、C组细胞因子无明显改变(P>0.05)。与D组相比,14d、21dA组视网膜SOCS1mRNA及蛋白表达降低(P<0.05),PBMC内SOCS1mRNA及蛋白无明显改变,B组、C组PBMC和视网膜内SOCS1mRNA及蛋白无明显改变。结论SOCS1反义寡核苷酸脂质体对EAU在眼部的炎症可能有一定的抑制作用。Objective Researches showed that suppressors of cytokine signaling（SOCS） are implicated in imnlunopathogenic mechanisms of autoimmune diseases. This study was to evaluate the effect of suppressor of cytokine signaling 1 （ SOCS1 ） antisense oligonucleotides on experimental antoimmune uveoretinitis （EAU）. Methods EAU was induced in 120 Lewis rats by immunizing using interphotoreeeptor retinoid-binding protein （IRBP）. Model rats were divided into four groups according to different agents of anterior cllamber injection：SOCS1 antisense oligonueleotide liposomes （group A） ,SOCS1 sense oligonucleotide liposomes（group B）,blank liposomes （group C）and saline buffer（ group D）. All immunized eyes were evaluated and ocular inflammation was graded based on slit-lamp microscope examination at 14,21,28 days after immunization, and retina and peripheral blood mononuclear cells（PBMC） of rats were subjected to analysis of SOCSlmRNA and protein expression using RTPCR and Western blot respectively. IL-4,IL-12 and IFN-γ in rat serum were detected by ELISA. Results In comparison with group A,aeute anterior uveitis was severer in group B ,C and D at 14 and 21 days after immunization. Ttle IL-12 and IFN-γ levels in rat serum were lower but IL-4 level was higher in group A than D at 14,21 days after immunization（ P 〈 0.05）. No significant differences were found in IL-4,IL-12 and IFN-γ production among the group B, C and D （ P 〉 0. 05 ）. Compared to group D, in group A,the expressions of SOCSlmRNA and protein in retina were decreased and the copies were 0.67 folds and 0.69 folds at 14 and 21 days in group A eompared with group D. There were not significant differences were found in expression of SOCS1 in peripheral blood nlononuclear cells and retina among group A, B, C and D （ P 〉 0.05 ）. Conclusion The injection of SOCS1 antisense oligonucleotide liposomes into the anterior chamber present with a prevention against EAU.

关 键 词：细胞因子信号抑制因子 实验性自身免疫性葡萄膜视网膜炎 反义寡核苷酸 

分 类 号：R774.1[医药卫生—眼科]