Struck H G, Giessler S, Giessler C
Klinik und Poliklinik für Augenheilkunde, Martin-Luther-Universität Halle-Wittenberg.
Ophthalmologe. 1995 Dec;92(6):849-53.
Previous investigations indicate that the application of a cyclooxygenase inhibitor alone can lead to amplification of the inflammatory process. To prevent this response a combination of flurbiprofen and leukotriene receptor antagonist (S 872419 A, Hoechst AG, Frankfurt/Main) were tested in an animal model. The right eye of 48 rabbits was burned with alcali (0.25 mol/l sodium hydroxide). Thirty animals were treated with (0.03% flurbiprofen sodium eye drops and 1% S872419 A eye drops, five times daily). Eighteen animals received no therapy for up to 14 days. Hyperemia of the limbal vessels, corneal vascularization, the number of PMNLs in the cornea and the prostacyclin level in the anterior chamber of the eye (ELISA) served as criteria. On day 3, after the chemical burn only the therapy group showed a significant decrease in hyperemia of the limbal vessels (14th day: score with therapy 0.3, without 2.17, P < 0.05). Without therapy corneal vascularization filled a much larger area from the 6th day on (14th day: area with therapy 3.5 mm2, without 63.7 mm2, P < 0.05). The number of PMNLs was effectively limited by therapy in the superficial stromal layers of the cornea and with therapy showed 2.4 cells/0.014 mm2 and without 18 cells/0.014 mm2 after 48 h. Without Therapy the level of prostacyclin was up to 15 times higher than with (12-h value with therapy) 607 pg/ml, without 9094 pg/ml, P < 0.05). Suppression of cyclo- and lipoxygenase-mediated inflammatory responses is possible with the combination of flurbiprofen and S 872419 A when two arachidonic by inhibition of prostanoid synthesis and leukotriene receptor block at the same time.
先前的研究表明,单独应用环氧化酶抑制剂可导致炎症过程的放大。为防止这种反应,在动物模型中测试了氟比洛芬和白三烯受体拮抗剂(S 872419 A,赫斯特股份公司,美因河畔法兰克福)的组合。用碱(0.25 mol/l氢氧化钠)烧伤48只兔子的右眼。30只动物接受(0.03%氟比洛芬钠滴眼液和1% S872419 A滴眼液治疗,每日5次)。18只动物长达14天未接受治疗。以角膜缘血管充血、角膜血管化、角膜中多形核白细胞数量以及眼前房中前列环素水平(酶联免疫吸附测定)作为标准。化学烧伤后第3天,仅治疗组角膜缘血管充血明显减轻(第14天:治疗组评分为0.3,未治疗组为2.17,P<0.05)。未治疗时,从第6天起角膜血管化面积更大(第14天:治疗组面积为3.5平方毫米,未治疗组为63.7平方毫米,P<0.05)。治疗有效限制了角膜浅层基质层中多形核白细胞的数量,治疗组48小时后显示为2.4个细胞/0.014平方毫米,未治疗组为18个细胞/0.014平方毫米。未治疗时,前列环素水平比治疗时高15倍(治疗组12小时值为607皮克/毫升,未治疗组为9094皮克/毫升,P<0.05)。当通过抑制前列腺素合成和同时阻断白三烯受体来抑制两种花生四烯酸时,氟比洛芬和S 872419 A的组合有可能抑制环氧化酶和脂氧化酶介导的炎症反应。