Kulkarni P S
Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Research Institute, University of Louisville School of Medicine.
J Ocul Pharmacol. 1994 Spring;10(1):329-34. doi: 10.1089/jop.1994.10.329.
Various classes of anti-inflammatory compounds like steroids (dexamethasone), cyclooxygenase inhibitors (indomethacin and flurbiprofen), 5-lipoxygenase inhibitors (BWA 218C and BWA 4C), immunosuppressive drugs (cyclosporin and rapamycin) and cod liver oil were tested for their antiinflammatory activities in endotoxin-induced uveitis model in rabbits. Intraocular inflammation was assessed in terms of two inflammatory responses i.e. breakdown of blood-aqueous barrier (BAB) and leukocyte infiltration into aqueous humor and iris ciliary body (ICB). Prostaglandin (PG) E2 and leukotriene (LT) B4 release into aqueous humor was also measured. Indomethacin significantly inhibited PGE2 release without affecting leukocyte or BAB response. Flurbiprofen prevented leukocyte, PGE2 and LTB4 release into aqueous humor but not ICB chemotaxis. BWA 218C and BWA 4C also significantly inhibited leukocyte and LTB4 release but not BAB responses. Dexamethasone (2mg/kg, i.m.) and cyclosporin A (25 mg/kg i.m.) significantly inhibited leukocyte infiltration into aqueous humor and ICB, and PGE2 release but they failed to inhibit breakdown of BAB and LTB4 release. On the other hand, rapamycin (10mg/kg i.m.) and cod liver oil (1 ml daily i.m. up to 15 days) significantly prevented leukocyte and BAB response. Cod liver oil also significantly inhibited PGE2 and LTB4 release but rapamycin affected only PGE2 release into aqueous humor. It is concluded that arachidonic acid metabolites may not play a vital role in this uveitis model and additional proinflammatory mediators like cytokines may be involved.
在兔内毒素诱导性葡萄膜炎模型中，对各类抗炎化合物进行了抗炎活性测试，这些化合物包括类固醇（地塞米松）、环氧化酶抑制剂（吲哚美辛和氟比洛芬）、5-脂氧合酶抑制剂（BWA 218C和BWA 4C）、免疫抑制药物（环孢素和雷帕霉素）以及鱼肝油。根据两种炎症反应对内眼炎症进行评估，即血-房水屏障（BAB）的破坏以及白细胞向房水和虹膜睫状体（ICB）的浸润。还测量了前列腺素（PG）E2和白三烯（LT）B4向房水的释放。吲哚美辛显著抑制PGE2的释放，但不影响白细胞或BAB反应。氟比洛芬可阻止白细胞、PGE2和LTB4释放到房水中，但不能阻止ICB趋化作用。BWA 218C和BWA 4C也显著抑制白细胞和LTB4的释放，但不影响BAB反应。地塞米松（2mg/kg，肌肉注射）和环孢素A（25mg/kg，肌肉注射）显著抑制白细胞浸润到房水和ICB中以及PGE2的释放，但它们未能抑制BAB的破坏和LTB4的释放。另一方面，雷帕霉素（10mg/kg，肌肉注射）和鱼肝油（每天1ml，肌肉注射，共15天）显著阻止白细胞和BAB反应。鱼肝油也显著抑制PGE2和LTB4的释放，但雷帕霉素仅影响PGE2向房水的释放。得出的结论是，花生四烯酸代谢产物在该葡萄膜炎模型中可能不发挥关键作用，可能涉及其他促炎介质如细胞因子。
