Suzuki Misa, Noda Kousuke, Kubota Shunsuke, Hirasawa Manabu, Ozawa Yoko, Tsubota Kazuo, Mizuki Nobuhisa, Ishida Susumu
Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Mol Vis. 2010 Jul 17;16:1382-8.
To investigate the effect of eicosapentaenoic acid (EPA) on acute ocular inflammation in an animal model of endotoxin-induced uveitis (EIU).
C57Bl/6 mice (6-week-old males) were orally treated with EPA at a dose of 50 mg/kg/day for 5 days. EIU was then induced in the animals by intraperitoneal injection of 160 microg lipopolysaccharide (LPS). Twenty-four hours after LPS injection, leukocyte adhesion to the retinal vasculature was evaluated by the concanavalin A lectin perfusion-labeling technique, and leukocyte infiltration into the vitreous cavity was quantified. Furthermore, the protein levels of monocyte chemotactic protein (MCP)-1, interleukin (IL)-6, intercellular adhesion molecule-1 and phospholyrated nuclear factor (NF)-kappaB p65 in the retina and retinal pigment epithelium (RPE)-choroid complex were examined by enzyme-linked immunosorbent assay (ELISA).
At 24 h after LPS injection, the EIU animals treated with oral EPA administration showed a significant decrease in leukocyte adhesion to the retinal vessels by 43.4% (p<0.01) and leukocyte infiltration into the vitreous cavity by 49.2% (p<0.05). In addition, EPA significantly reduced the protein levels of MCP-1 and IL-6 in the retina and the RPE-choroid complex. Furthermore, phosphorylation of NF-kappaB was suppressed by EPA treatment.
Our data suggest that EPA inhibits multiple inflammatory molecules in vivo. EPA may become a novel strategy in the prevention and/or treatment of ocular inflammatory diseases.
在内毒素诱导的葡萄膜炎(EIU)动物模型中研究二十碳五烯酸(EPA)对急性眼部炎症的影响。
对6周龄雄性C57Bl/6小鼠口服给予剂量为50 mg/kg/天的EPA,持续5天。然后通过腹腔注射160微克脂多糖(LPS)诱导动物发生EIU。LPS注射24小时后,采用伴刀豆球蛋白A凝集素灌注标记技术评估白细胞对视网膜血管的黏附情况,并对进入玻璃体腔的白细胞浸润进行定量分析。此外,通过酶联免疫吸附测定(ELISA)检测视网膜和视网膜色素上皮(RPE)-脉络膜复合体中单核细胞趋化蛋白(MCP)-1、白细胞介素(IL)-6、细胞间黏附分子-1和磷酸化核因子(NF)-κB p65的蛋白水平。
LPS注射后24小时,口服EPA处理的EIU动物显示白细胞对视网膜血管的黏附显著降低43.4%(p<0.01),进入玻璃体腔的白细胞浸润显著降低49.2%(p<0.05)。此外,EPA显著降低了视网膜和RPE-脉络膜复合体中MCP-1和IL-6的蛋白水平。而且,EPA处理抑制了NF-κB的磷酸化。
我们的数据表明EPA在体内抑制多种炎症分子。EPA可能成为预防和/或治疗眼部炎症性疾病的一种新策略。