砒石对哮喘小鼠白三烯B4 及5-脂氧合酶基因表达的影响

目的: 探讨白三烯B4 (LTB4) 水平、5-脂氧合酶(5-LO) 基因表达在小鼠哮喘发病中的作用以及砒石(arsenolite, As) 对哮喘的治疗作用与LTB4 水平及5-LO 基因表达的关系。方法: 建立小鼠卵蛋白哮喘模型, 灌胃给予砒石等药, 用ELISA 的方法检测支气管肺泡灌洗液(BALF) LTB4 含量;用RT-PCR 的方法检测肺组织中5-LO mRNA 表达的变化。结果: 哮喘小鼠BALF 中LTB4 水平、肺组织5-LO 基因表达水平较正常对照组显著升高。4 种剂量的砒石均可抑制哮喘小鼠BALF 中LTB4 的水平, 均能降低哮喘小鼠5-LO mRNA 表达的量。其中砒石5.00 mg·kg^-1 剂量的效果优于砒石0.625 mg·kg^-1剂量的效果。结论: LTB4 在气道中的高水平, 5-LO 基因表达的上调在OVA 致敏小鼠的哮喘发病中起重要作用。砒石可显著降低哮喘小鼠BALF 中LTB4 水平, 抑制哮喘小鼠肺组织中5-LO 基因的表达, 从而表现出抗哮喘的活性。

Effects of arsenolite on leukotriene B4 and genic expression of 5-lipoxygenase in asthmatic mice

AIM: To investigate the role of leukotriene B4 (LTB4) and the expression of 5-lipoxygenase (5-LO) in ovalbumin-induced asthmatic mice and study the effect of arsenolite on LTB4 and the expression of 5-LO in those mice as well as the mechanism of arsenolite inhibiting asthma.METHODS: The mice were challenged with saline or OVA and ig with saline, mung bean, dexamethasone or arsenolite (0.625, 1.25, 2.50, 5.00mg·kg^-1) twice daily for 3 days.The LTB4 of BALF was measured by ELISA and RT-PCR was used to detect the mRNA expression of 5-LO in pulmonary tissue.RESULTS: The levels of LTB4 in BALF and 5-LO mRNA expression in pulmonary tissue of asthmatic group significantly increased compared with normal group.The levels of LTB4 in BALF and 5-LO mRNA expression in lung tissue in groups treated with 4 doses arsenolite were significantly lower than those in asthmatic group.Moreover, the 5-LO mRNA in group As 5.00 was significantly lower than that in group As 0.625.CONCLUSION: The high level of LTB4 in BALF, up-regulation of 5-LO mRNA in pulmonary tissue play very important roles in bronchial asthma.Arsenolite can efficiently treat asthma.Its mechanism maybe partly relates to the decrease of LTB4 in airway and the inhibitions of the mRNA expression of 5-Lo in pulmonary tissue.