三氮脒减轻内毒素诱导性小鼠葡萄膜炎的研究  

Diminazene aceturate ameliorates endotoxin-induced uveitis in mice

作　　者：邱一果[1] 杨红霞[1] 杨培增[1] 雷博[1] 

机构地区：[1]重庆医科大学附属第一医院眼科眼科学重庆市重点实验室重庆市眼科研究所,重庆400016

出　　处：《第三军医大学学报》2013年第20期2195-2198,共4页Journal of Third Military Medical University

基　　金：国家自然科学基金面上项目(30973251,81271033)~~

摘　　要：目的探讨三氮脒(diminazene aceturate,DIZE)是否能减轻内毒素诱导性小鼠葡萄膜炎。方法连续给予一般情况良好、体质量16～20 g的雌性BALB/c小鼠腹腔内注射DIZE(60 mg/kg)2 d后,将125 ng脂多糖(lipopolysaccharides,LPS)注射入小鼠玻璃体内建立内毒素诱导性葡萄膜炎模型。分别于注射LPS后12、24 h观察小鼠眼前房炎症情况并进行临床评分。第24小时摘除眼球,石蜡切片HE染色观察小鼠眼部形态学变化。用Real-time PCR检测小鼠眼内炎症细胞因子表达。结果在注射LPS 12 h后DIZE对眼前房炎症出现明显的保护作用。24 h时DIZE+LPS组的临床评分[(1.75±0.96)分]明显低于生理盐水+LPS组[(4.00±1.22)分](P<0.01);HE染色结果显示DIZE+LPS组小鼠玻璃体内渗出的炎症细胞数明显少于生理盐水+LPS组,但各组小鼠视网膜结构和层次无明显改变。DIZE+LPS组的小鼠眼内细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)、TNF-α、单核细胞趋化蛋白(monocyte chemoattractant protein-1,MCP-1)、IL-6的mRNA水平明显低于生理盐水+LPS组(P<0.01)。结论 DIZE在LPS引起的内毒素诱导性小鼠葡萄膜炎的眼部炎症中起保护作用,有望成为一种治疗葡萄膜炎的新药。Objective To investigate whether diminazene aceturate （DIZE） protects mice from endotoxin-induced uveitis （EIU）. Methods Female BALB/c mice received intraperitoneal injection of DIZE （60 mg/kg） for 2 d prior to intravitreous injection of lipopolysaccharides （LPS, 125 ng）. The anterior segments of the mice were examined and clinical scores were determined at 12 and 24 h after LPS injection. Morphology change was evaluated with a light microscope at 24 hours after LPS injection. The mRNA levels of inflammatory cytokines in the eyes were measured by real-time PCR. Results At the 24th hour, the clinical score of mice treated with DIZE （1.75±0.96） was significantly lower than that of the saline-injected controls （4.00±1.22, P〈0.01）. Histological examination showed the total infiltrating inflammatory cells remarkably reduced in DIZE-treated eyes. The mRNA levels of ICAM-1, TNF-α, MCP-1, and IL-6 were significantly reduced in DIZE-treated eyes（P〈0.01）. Conclusion DIZE protects retinal structure and reduces infiltrating inflammatory cells in LPS-induced EIU mouse model. These results support that DIZE may provide a novel therapeutic strategy for uveitis.

关 键 词：三氮脒 小鼠 内毒素诱导性葡萄膜炎 细胞因子 炎症 

分 类 号：R-332[医药卫生] R773.905