肿瘤坏死因子α反义寡核苷酸对内毒素诱导的葡萄膜炎的抑制作用  

Inhibitory Effects of Subconjunctival Antisense Oligonucleotides Targeting TNF-α on Endotoxin-induced Uveitis

作　　者：李劲[1,2] 宋琳 彭伟[1,2] 朱格非[1,2] 胡慧丽 聂爱芹 

机构地区：[1]暨南大学第二临床医学院 [2]深圳市人民医院眼科,深圳518020 [3]华中科技大学同济医学院附属同济医院眼科,武汉430030

出　　处：《华中科技大学学报（医学版）》2010年第4期506-509,共4页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：深圳市科技计划资助项目(No.200803098)

摘　　要：目的观察局部使用肿瘤坏死因子α反义寡核苷酸(TNF-α-ASON)对内毒素诱导的葡萄膜炎(EI U)的影响。方法将TNF-α-ASON(实验组)和PBS(对照组)于建立EI U模型前48 h和0 h注射于小鼠结膜下,建模后6、12、24 h通过手术显微镜对两组小鼠眼部的炎症病变进行临床评分;制作眼部组织切片并通过显微镜进行炎性细胞计数;利用ELISA试剂盒测定24 h眼内TNF-α含量。另外,观察结膜下注射的荧光素标记的TNF-α-ASON在眼内的分布。结果与对照组相比,实验组葡萄膜炎临床评分显著降低(P<0.01);前房、虹膜、睫状体及玻璃体内炎性细胞计数实验组较对照组显著减少(P<0.01);注射TNF-α-ASON后实验组眼内TNF-α含量显著降低。结膜下注射7 d后,脉络膜和视网膜上仍然可以观察到TNF-α-ASON。结论采用TNF-α-ASON可以显著降低EI U小鼠眼内TNF-α含量,减轻眼内葡萄膜炎反应。结膜下注射是一种安全有效的基因治疗给药途径。Objective To investigate the effect of subconjunctival antisense oligonucleotides targeting TNF-α（TNF-α- ASON）on endotoxin induced uveitis（EIU）. Methods TNF a ASON and PBS were respectively injected subconjunctivally 48 and 0h before establishment of EIU. The clinical score was assessed according to the binocular operation microscope at 6,12,24 h after EIU establishment in mice. Ocular inflammatory cell infiltration was observed histologically Under a microscr）pe. The contents of TNF-α were measured by enzyme-linked immunosorbent assay（ELISA）. In vivo Uptake was determined after subconjunctival injeclion of FITC-labeled TNF a ASON. Results TNF a ASON injection reduced the incidence and Severity of u veitis and the inflammatory cell infiltration in anterior chamber,iris,ciliary body and vitreous cavity, at 24 h（P.〈0.01）. The ex pression of TNF-a was also decreased after subconjunctival injection. In vivo ,FITC TNF a ASON was found in the eye up to 7 days after subconjunctival injection. Conclusion Topical TNF-α-ASON injection reduced the contents of TNF-α and the incidence of uveitis. Subconjunctival injection is a useful and safe approach for gene therapy.

关 键 词：肿瘤坏死因子 反义寡核苷酸 葡萄膜炎 

分 类 号：R773[医药卫生—眼科]