Ilieva Iliyana, Ohgami Kazuhiro, Jin Xue-Hai, Suzuki Yukari, Shiratori Kenji, Yoshida Kazuhiko, Kase Satoru, Ohno Shigeaki
Department of Ophthalmology and Visual Sciences, Hokkaido University Graduate School of Medicine, N15 W7 Kita-ku, Sapporo 060-8638, Japan.
Exp Eye Res. 2006 Sep;83(3):651-7. doi: 10.1016/j.exer.2006.03.005. Epub 2006 May 12.
Captopril is an inhibitor of angiotensin-converting enzyme (ACE) that is largely used in the treatment of cardiovascular diseases. Several previous studies have demonstrated that captopril exhibits a wide variety of biological activities, including an anti-inflammatory action, on which we focused our attention. The aim of the present study was to investigate the efficacy of captopril on endotoxin induced uveitis (EIU) in rats. We investigated its effect upon cellular infiltration and protein leakage, as well as on the concentration of tumor necrosis factor-alpha (TNF-alpha), nitric oxide (NO), prostaglandin E2 (PGE2), monocyte chemoattractant protein-1 (MCP-1) in the anterior chamber. In addition, we checked its effect on activation of nuclear factor kappa B (NF-kappaB) in iris and ciliary body (ICB) cells in vivo. EIU was induced in male Lewis rats by a footpad injection of lipopolysaccharide (LPS). One hour after the LPS inoculation, either 1mg/kg, 10mg/kg or 100mg/kg captopril were injected intravenously. 24h later, the aqueous humor was collected from both eyes, and the number of infiltrating cells and protein concentration in the aqueous humor were determined. Levels of TNF-alpha, PGE2, NO and MCP-1 were determined by enzyme-linked immunosorbent assay. On some eyes, after enucleation, immunohistochemical staining with a monoclonal antibody against activated NF-kappaB was performed. Captopril treatment significantly decreased the inflammatory cells infiltration, the level of protein, concentrations of TNF-alpha, PGE2, NO and MCP-1 in the aqueous humor. The number of activated NF-kappaB-positive cells was lower in ICB of the rats treated with captopril 3h after the LPS injection. The present results indicate that captopril suppresses the inflammation in EIU by inhibiting the NF-kappaB-dependent pathway and the subsequent production of pro-inflammatory mediators.
卡托普利是一种血管紧张素转换酶（ACE）抑制剂，广泛用于治疗心血管疾病。先前的多项研究表明，卡托普利具有多种生物学活性，包括抗炎作用，我们将注意力集中于此。本研究的目的是探讨卡托普利对大鼠内毒素诱导性葡萄膜炎（EIU）的疗效。我们研究了其对细胞浸润和蛋白质渗漏的影响，以及对前房内肿瘤坏死因子-α（TNF-α）、一氧化氮（NO）、前列腺素E2（PGE2）、单核细胞趋化蛋白-1（MCP-1）浓度的影响。此外，我们还检查了其对体内虹膜和睫状体（ICB）细胞中核因子κB（NF-κB）激活的影响。通过足垫注射脂多糖（LPS）在雄性Lewis大鼠中诱导EIU。LPS接种1小时后，静脉注射1mg/kg、10mg/kg或100mg/kg卡托普利。24小时后，从双眼收集房水，测定房水中浸润细胞的数量和蛋白质浓度。通过酶联免疫吸附测定法测定TNF-α、PGE2、NO和MCP-1的水平。在一些眼睛摘除后，用抗活化NF-κB的单克隆抗体进行免疫组织化学染色。卡托普利治疗显著减少了炎症细胞浸润、房水中蛋白质水平、TNF-α、PGE2、NO和MCP-1的浓度。LPS注射3小时后，用卡托普利治疗的大鼠ICB中活化的NF-κB阳性细胞数量较少。目前的结果表明，卡托普利通过抑制NF-κB依赖性途径和随后促炎介质的产生来抑制EIU中的炎症。
