【摘要】 为探讨血小板活化因子选择性拮抗剂ＯＮＯ－６２４０治疗哮喘患者的临床应用价值，应用鸡卵清蛋白致敏和刺激小鼠复制过敏性哮喘模型，研究ＯＮＯ－６２４０对抗原引起气道嗜酸性粒细胞（ＥＯＳ）浸润的影响。结果表明，正常小鼠支气管肺泡冲洗液中未见到ＥＯＳ；致敏小鼠给予抗原反复吸入刺激后，支气管肺泡冲洗液（ＢＡＬＦ）中ＥＯＳ急剧增多（９．６８×１０￣８／Ｌ±０．７２×１０￣８／Ｌ）。在（ＯＮＯ－６２４０治疗各组中，ＯＮＯ－６２４０的剂量０．１ｍｇ／ｋｇ、１．０ｍｇ／ｋ及１０．０ｍｇ／ｋｇ分别导致ＥＯＳ数下降４２．１％（５．６０×１０￣８／Ｌ±０．９７×１０￣８／Ｌ，Ｐ＜０．０１）、５８．８％（３．９９×１０￣８／Ｌ±０．８４×１０￣８／Ｌ，Ｐ＜０．０１）及７２．６％（２．６５×１０￣８／Ｌ±０．７１×１０￣８／Ｌ，Ｐ＜０．０１）。还发现ＯＮＯ－６２４０抑制ＥＯＳ对气道的浸润伴随着白细胞介素（ＩＬ－５和ＩＬ－２）水平的明显降低。这些结果提示，ＯＮＯ－６２４０通过抑制ＩＬ－５和ＩＬ－２的产生，从而抑制了ＥＯＳ在气道的聚集；认为ＯＮＯ－６２４０用于哮喘患者的临床治疗理应取得较好的疗效。更多还原

【Abstract】 n in vivo mouse model of allergic bronchial asthma was developed to investigate the effects of a platelet-activating factor antagonist ONO-6240 on eosinophil(EOS)recruitment into the mouse airway.In the present study,no EOS could be found in bronchoalveolar lavage fluid(BALF)from normal control mice.However,chronic ovalbumin challenge of sensitized mice induced significant bronchoalveolar eosinophilia(9.68±0.72×10￣8/L).In three groups of mice treated intraperioneally with different doses ofONO-6240(0.1,1.0, 10.0mg/kg),the medication produced 42.1%(5.60±0. 97× 10￣8/L,P<0.01),58.8%(3.99±0. 84± 10￣8/L,P<0.01),and 72.6%(2. 65±0.71× 10￣8/L,P<0. 01) inhibition,re-spectively, of the antigen-induced influx of EOS into BALF. It was found that the prevention of EOS infil-tration into airway with ONO-6240 was accompanied by decrements of both interleukin(IL )-5 and IL- 2levels. These data indicated that ONO-6240 prevented airway eosinophilia by inhibiting prduction of IL-5and IL-2, Our results suggented that ONO-6240 may be of value in treating human asthmatic patients.更多还原