Eicosapentaenoic acid is anti-inflammatory in preventing choroidal neovascularization in mice
Eicosapentaenoic acid is anti-inflammatory in preventing choroidal neovascularization in mice
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DOI：
10.1167/iovs.06-1148
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发表时间：
2007-09-01
影响因子：
4.4
通讯作者：
Ishida, Susumu
中科院分区：
文献类型：
--
作者：
Koto, Takashi;Nagai, Norihiro;Ishida, Susumu
目的：研究二十碳五烯酸（EPA），即主要的ω - 3多不饱和脂肪酸（PUFA），在脉络膜新生血管形成（CNV）发展中的作用以及潜在的分子机制。
方法：给6周龄的C57BL / 6小鼠喂食含5% EPA或ω - 6 PUFA亚油酸（LA）的实验室饲料，持续4周。进行激光光凝诱导CNV，并通过体积测量评估CNV组织的体积。通过逆转录聚合酶链反应（RT - PCR）和酶联免疫吸附测定（ELISA）评估体内视网膜色素上皮（RPE） - 脉络膜中细胞间黏附分子（ICAM） - 1、单核细胞趋化蛋白（MCP） - 1、血管内皮生长因子（VEGF）和白细胞介素（IL） - 6的表达和产生，以及体外刺激的b - End3内皮细胞和RAW264.7巨噬细胞中的相关情况。分别通过气相色谱法和高效液相色谱法分析血清和RPE - 脉络膜中的脂肪酸组成。通过ELISA检测血清中C - 反应蛋白（CRP）、IL - 6、VEGF、MCP - 1和可溶性ICAM - 1的水平。
结果：与对照小鼠相比，喂食EPA的动物的CNV体积显著受到抑制，而富含LA的饮食不影响CNV。在补充EPA的小鼠中，CNV诱导后ICAM - 1、MCP - 1、VEGF和IL - 6的mRNA表达和蛋白质水平显著降低。在体外，应用EPA显著抑制内皮细胞中ICAM - 1和MCP - 1以及巨噬细胞中VEGF和IL - 6的mRNA和蛋白质水平。喂食EPA的小鼠在血清和RPE - 脉络膜中表现出比对照动物显著更高的EPA水平和更低的ω - 6 PUFA花生四烯酸水平。在CNV诱导后，EPA补充还导致血清中IL - 6和CRP水平显著降低。
结论：本研究首次表明富含EPA的饮食在体内和体外均可显著抑制CNV以及与CNV相关的炎症分子。这些结果表明，经常摄入ω - 3 PUFA可能预防CNV，并降低因年龄相关性黄斑变性导致失明的风险。
PURPOSE. To investigate the role of eicosapentaenoic acid (EPA), the major omega-3 polyunsaturated fatty acid (PUFA), in the development of choroidal neovascularization (CNV), together with underlying molecular mechanisms.METHODS. Six-week-old C57BL/ 6 mice were fed with laboratory chow with 5% EPA or the omega-6 PUFA linoleic acid ( LA) for 4 weeks. Laser photocoagulation was performed to induce CNV, and the volume of CNV tissue was evaluated by volumetric measurements. The expression and production of intercellular adhesion molecule (ICAM)-1, monocyte chemotactic protein (MCP)-1, vascular endothelial growth factor ( VEGF) and interleukin (IL)-6 in the retinal pigment epithelium (RPE)-choroid in vivo, and stimulated b-End3 endothelial cells and RAW264.7 macrophages in vitro were evaluated by RT-PCR and ELISA. Fatty acid composition in the serum and the RPE-choroid was analyzed by gas chromatography and high-performance liquid chromatography, respectively. Serum levels of C-reactive protein (CRP), IL-6, VEGF, MCP-1, and soluble ICAM-1 were examined by ELISA.RESULTS. The CNV volume in EPA-fed animals was significantly suppressed compared with that in control mice, whereas the LA-rich diet did not affect CNV. The mRNA expression and protein levels of ICAM- 1, MCP-1, VEGF, and IL- 6 after CNV induction were significantly reduced in EPA-supplemented mice. In vitro, EPA application led to significant inhibition of mRNA and protein levels of ICAM- 1 and MCP-1 in endothelial cells and VEGF and IL- 6 in macrophages. EPA- fed mice exhibited significantly higher levels of EPA and lower levels of the omega-6 PUFA arachidonic acid in the serum and the RPE-choroid than control animals. EPA supplementation also led to significant reduction of serum levels of IL- 6 and CRP after CNV induction.CONCLUSIONS. The present study demonstrates for the first time that an EPA- rich diet results in significant suppression of CNV and CNV-related inflammatory molecules in vivo and in vitro. These results suggest that frequent consumption of omega-3 PUFAs may prevent CNV and lower the risk of blindness due to age-related macular degeneration.