【摘要】 目的:观察新型非甾体抗炎药2-(2,4-二氯苯基)-3-(3,5-二甲氧基苯基)-苯丙烯酰胺(AL-017)对诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)及环氧化酶2(cyclooxygenase-2,COX-2)的抑制作用,探讨其分子机制。方法:体外培养小鼠巨噬细胞(RAW264.7),用脂多糖(LPS)刺激,观察AL-017对一氧化氮(nitrogen monoxidum,NO)释放、iNOS总酶活、iNOS及COX-2的mRNA表达水平、p38信号通路有无影响。结果:AL-017可以显著抑制LPS引起的NO的释放,使LPS刺激下增高的iNOS酶活性降低,同时显著下调LPS诱导的iNOS及COX-2 mRNA表达水平的升高,并可明显抑制LPS刺激下p38丝裂原活化蛋白激酶(p38MAPK)的磷酸化。结论:AL-017可有效抑制LPS引起的小鼠巨噬细胞炎症反应,其抗炎机制可能与抑制p38MAPK磷酸化有关。更多还原

【Abstract】 Objective:To investigate the inhibitory effect of AL-017 on inducible nitric oxide synthase(iNOS) and cyclooxygenase-2(COX-2) and its possible molecular mechanism.Methods:Mouse macrophages(RAW264.7) were stimulated by lipopolysaccharide(LPS).NO release,total iNOS enzyme activity,mRNA expression levels of iNOS and COX-2,and p38 MAPK were analyzed after LPS stimulation.Results:AL-017(3μmol·L-1) decreased the LPS-induced NO production and increased iNOS activity with inhibitory rates of 77.2% and 70.0%,respectively.AL-017 also significantly reduced LPS-stimulated increases in iNOS and COX-2 mRNA,and p38 MAPK phosphorylation.Conclusion:AL-017 can prevent LPS-stimulated inflammation in RAW264.7 cells,which may be associated with the inhibition of p38 MAPK phosphorylation.更多还原