Inhibitory Effect of Aminoimidazole Carboxamide Ribonucleotide (AICAR) on Endotoxin-Induced Uveitis in Rats
Inhibitory Effect of Aminoimidazole Carboxamide Ribonucleotide (AICAR) on Endotoxin-Induced Uveitis in Rats
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DOI：
10.1167/iovs.11-7331
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发表时间：
2011-08-01
影响因子：
4.4
通讯作者：
Vavvas, Demetrios G.
中科院分区：
文献类型：
--
作者：
Suzuki, Jun;Manola, Akrivi;Vavvas, Demetrios G.
目的.目的探讨腺苷酸（AMP）类似物氨基咪唑甲酰胺核苷酸（AICAR）对内毒素诱导的葡萄膜炎（EIU）的抗炎作用。在刘易斯大鼠中通过皮下注射脂多糖（LPS）（200 μ g）诱导EIU。AICAR（50 mg/kg，腹腔内）在LPS注射前6小时和注射LPS的同时给予。24小时后测量临床葡萄膜炎评分、前房（AC）浸润细胞数、前房蛋白浓度、视网膜血管白细胞粘附和蛋白渗漏。采用酶联免疫吸附试验（ELISA）检测各组大鼠房水和视网膜中C-C趋化因子配体2（CCL-2）/单核细胞趋化蛋白1（MCP-1）、肿瘤坏死因子-α（TNF-α）和细胞间粘附分子1（ICAM-1）的蛋白水平，以及视网膜中核因子-κ B（NF-κ B）的核转位。外周血单个核细胞中CD 14的mRNA和蛋白水平也被测量。AICAR治疗显著降低了EIU的临床严重程度以及炎性细胞浸润和房水中的蛋白浓度。同样，AICAR治疗减少了视网膜血管粘附白细胞和蛋白渗漏的数量。AICAR治疗抑制了房水中TNF-α、CCL-2/MCP-1和ICAM-1的蛋白水平以及视网膜中CCL-2/MCP-1和ICAM-1的水平。AICAR还降低NF-κ B易位和CD 14表达。AICAR通过限制白细胞浸润、抑制炎症介质和抑制NF-κ B通路降低大鼠EIU模型中全身性LPS易感性并减轻眼内炎症。（Invest Ophthalmol维斯科学。2011; 52：6565-6571）DOI：10.1167/iovs.11-7331
PURPOSE. To investigate the anti-inflammatory effect of aminoimidazole carboxamide ribonucleotide (AICAR), an analog of adenosine monophosphate (AMP), in endotoxin-induced uveitis (EIU).METHODS. EIU was induced by subcutaneous injection of lipopolysaccharide (LPS) (200 mu g) in Lewis rats. AICAR (50 mg/kg, intraperitoneally) was given 6 hours prior and at the same time as LPS injection. Clinical uveitis scores, number of anterior chamber (AC) infiltrating cells, anterior chamber protein concentration, retinal vessel leukocyte adhesion, and protein leakage were measured 24 hours later. Protein levels of C-C chemokine ligand-2 (CCL-2)/monocyte chemotactic protein-1 (MCP1), tumor necrosis factor-alpha (TNF-alpha) and intercellular adhesion molecule-1 (ICAM-1) in aqueous humor and retina and nuclear translocation of nuclear factor-kappa B (NF-kappa B) in the retina were determined by enzyme-linked immunosorbent assay (ELISA). Both mRNA and protein levels of CD14 in peripheral blood mononuclear cells were also measured.RESULTS. AICAR treatment significantly reduced EIU clinical severity as well as inflammatory cell infiltration and protein concentration in aqueous humor. Similarly, the number of retinal vessel-adherent leukocytes and protein leakage were decreased by AICAR treatment. Protein levels of TNF-alpha, CCL-2/MCP-1, and ICAM-1 in aqueous humor and CCL-2/MCP-1 and ICAM-1 levels in retina were suppressed with AICAR treatment. AICAR also reduced NF-kappa B translocation and CD14 expression.CONCLUSIONS. AICAR reduces systemic LPS susceptibility and attenuates intraocular inflammation in a rat EIU model by limiting infiltration of leukocytes, suppressing inflammatory mediators, and inhibiting the NF-kappa B pathway. (Invest Ophthalmol Vis Sci. 2011; 52: 6565-6571) DOI: 10.1167/iovs.11-7331