血小板活化因子拮抗剂对抗原引起气道嗜酸性粒细胞浸润的影响

Effects of antagonists for platelet activeating factor on antigen induced eosinophil infiltration into the airway

为探讨血小板活化因子（ＰＡＦ）拮抗剂消除哮喘气道炎症的价值，应用鸡卵清蛋白致敏和刺激小鼠复制过敏性气道炎症模型，研究ＰＡＦ拮抗剂对于抗原引起气道嗜酸性粒细胞（ＥＯＳ）浸润的影响。体内实验结果表明，正常小鼠支气管肺泡灌洗液（ＢＡＬＦ）中未见到ＥＯＳ；致敏小鼠给予抗原多次反复吸入刺激后，ＢＡＬＦ中ＥＯＳ急剧增多。在ＰＡＦ一种选择性拮抗剂ＹＭ－２６４治疗各组中，ＹＭ－２６４的不同剂量０．１ｍｇ／ｋｇ、１．０ｍｇ／ｋｇ及１０ｍｇ／ｋｇ分别导致ＥＯＳ数下降２７．０％，４８．２％及６７．９％。还发现ＹＭ－２６４抑制ＥＯＳ对气道的浸润还伴随着脾脏细胞培养上清液中白细胞介素５（ＩＬ－５）水平的明显降低。体外实验结果表明，ＰＡＦ另一种选择性拮抗剂ＯＮＯ－６２４０于体外培养时能抑制淋巴细胞产生ＩＬ－５并呈明显的剂量相关性，而这种抑制作用至少可以维持７２小时。这些结果提示ＰＡＦ拮抗剂通过抑制ＩＬ－５的产生从而抑制了ＥＯＳ在气道的聚集。认为ＰＡＦ拮抗剂用于临床治疗支气管哮喘患者理应取得较好的疗效。

To investigate the values of antagonists for platelet activating factor(PAF) on eliminating asthmatic airway inflammation,a mouse model of allergic bronchial inflammation was developed to explore the effects of PAF antagonist on eosinophil recruitment into the mouse airway.In the in vivo experiments,no eosinophils could be found in bronchoalveolar lavage fluid (BALF) from normal control mice.However,chronic ovalbumin challenge of sensitized mice induced significant bronchoalveolar eosinophilia.In mice treated with intraperitoneal injection of YM 264 before each challenge,compared with the data of positive control different doses of YM 264 (0.1mg/kg,1.0mg/kg and 10.0mg/kg) decreaced the number of eosinophils by 27.0%,48.2% and 67.9%,respectively.It was found that the prevention of eosinophil infiltration into airway with YM 264 was accompanied by the decrease of interleukin (IL) 5 levels.Besides,the results of the in vitro experiments demonstrated that cultured lymphocytes treated with ONO 6240 released much lower levels of IL 5 than those without NON 6240,and this inhibition could last no less than 72 hours.All these data indicated that PAF antagonists prevented airway eosinophilia by inhibiting production of IL 5.Our results suggest that PAF antagonists may be of value in treating human asthmatic patients.