Ferrari A. J.L., Van Linthoudt D., Morrone L., Branigan P., Schumacher H. R., Baker D. G.
The Arthritis--Immunology Center and Veterans Affairs Medical Center, Philadelphia, USA.
Am J Ther. 1996 Mar;3(3):189-194.
The objective of this study was to determine the effects of orally administered misoprostol and diclofenac on inflammation caused by particulates in the rat subcutaneous air-pouch model. Subcutaneous air pouches were formed in male Sprague-Dawley rats. The animals were premedicated by gavage with either saline, diclofenac, misoprostol, or both diclofenac and misoprostol. The air pouches were injected with either polymethyl methacrylate particles or monosodium urate crystals, and the pouch fluids were obtained at 1, 6, 24, 48, and 72 h. Leukocyte influx, tumor necrosis factor, neutral metalloprotease activity, and prostaglandin E(2) levels were measured. It was determined that leukocyte influx was inhibited by diclofenac in the acute inflammation caused by monosodium urate crystals only. In all animals receiving diclofenac, prostaglandin E(2) (PGE(2)) levels were reduced, whereas tumor necrosis factor levels were elevated. The elevation of tumor necrosis factor was prevented by the addition of misoprostol. It is concluded that the oral administration of diclofenac or misoprostol can affect levels of specific mediators involved in particulate-induced inflammation in the subcutaneous air pouch.
本研究的目的是确定口服米索前列醇和双氯芬酸对大鼠皮下气囊模型中颗粒引起的炎症的影响。在雄性斯普拉格-道利大鼠中形成皮下气囊。动物通过灌胃预先给予生理盐水、双氯芬酸、米索前列醇或双氯芬酸与米索前列醇两者。向气囊中注射聚甲基丙烯酸甲酯颗粒或尿酸钠晶体，并在1、6、24、48和72小时获取囊液。测量白细胞流入、肿瘤坏死因子、中性金属蛋白酶活性和前列腺素E(2)水平。结果确定，仅在尿酸钠晶体引起的急性炎症中，双氯芬酸抑制白细胞流入。在所有接受双氯芬酸的动物中，前列腺素E(2)（PGE(2)）水平降低，而肿瘤坏死因子水平升高。添加米索前列醇可防止肿瘤坏死因子升高。结论是，口服双氯芬酸或米索前列醇可影响皮下气囊中颗粒诱导的炎症中涉及的特定介质水平。
