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环氧化酶-2在大鼠变应性鼻炎中的作用

Involvement of cyclooxygenase-2 in allergic nasal inflammation in rats.

作者信息

Rahman Ashequr, Yatsuzuka Rie, Jiang Shuishi, Ueda Yuhki, Kamei Chiaki

机构信息

Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan.

出版信息

Int Immunopharmacol. 2006 Nov;6(11):1736-42. doi: 10.1016/j.intimp.2006.07.009. Epub 2006 Aug 2.

Abstract

This study was undertaken to investigate the involvement of cyclooxygenase-2 (COX-2) in allergic nasal inflammation in actively sensitized rats. An allergic rhinitis model was developed by the repeated topical application of antigen into the nasal cavities in the sensitized rats. The severity of allergic rhinitis was studied by measuring the nasal behavior, as well as electroencephalogram (EEG) activity by antigen challenge. The electrodes were implanted chronically into the bilateral olfactory bulb of the rats and the EEG was measured monopolarly with an electroencephalograph (EEG, Nohon Kohden, Japan). The intranasal application of antigen caused the increase of nasal allergic signs as well as an EEG spike in a dose-dependent fashion, and at a dose of 50 microg/site, it showed a significant effect. The responses induced by the antigen were evaluated with certain drugs, etodolac (a selective COX-2 inhibitor), indomethacin (a non-selective COX inhibitor), ramatroban (a thromboxane A2 receptor antagonist) and zafirlukast (a cys-leukotriene receptor antagonist). Etodolac showed the inhibition of nasal behavior and EEG spike in a dose-related fashion, and at doses of 3 and 10 mg/kg, it showed a significant effect. Moreover, ramatroban also caused the dose-related inhibition of nasal behavior and EEG spike induced by antigen. On the other hand, both indomethacin and zafirlukast had no effects on the responses induced by antigen, even at a higher dose. Therefore, it can be concluded that cyclooxygenase-2 actively participates in the allergic nasal inflammation in actively sensitized rats.

摘要

本研究旨在探讨环氧化酶-2(COX-2)在主动致敏大鼠变应性鼻炎中的作用。通过在致敏大鼠鼻腔反复局部应用抗原建立变应性鼻炎模型。通过测量鼻腔行为以及抗原激发后的脑电图(EEG)活动来研究变应性鼻炎的严重程度。将电极长期植入大鼠双侧嗅球,用脑电图仪(EEG,日本光电)单极记录EEG。鼻内应用抗原可引起鼻腔变应性体征增加以及EEG尖峰,呈剂量依赖性,在50μg/部位的剂量下有显著作用。用某些药物评估抗原诱导的反应,依托度酸(一种选择性COX-2抑制剂)、吲哚美辛(一种非选择性COX抑制剂)、雷马曲班(一种血栓素A2受体拮抗剂)和扎鲁司特(一种半胱氨酰白三烯受体拮抗剂)。依托度酸呈剂量依赖性抑制鼻腔行为和EEG尖峰,在3和10mg/kg剂量时有显著作用。此外,雷马曲班也呈剂量依赖性抑制抗原诱导的鼻腔行为和EEG尖峰。另一方面,吲哚美辛和扎鲁司特即使在高剂量时对抗原诱导的反应也无影响。因此,可以得出结论,环氧化酶-2在主动致敏大鼠变应性鼻炎中起积极作用。

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