来氟米特抑制PAF诱导的兔滑膜细胞DNA合成及PAF自大鼠腹腔巨噬细胞中产生

LEFLUNOMIDE INHIBITS PAF INDUCED DNA SYNTHESIS IN RABBIT SYNOVIAL CELLS AND PAF PRODUCTION FROM RAT PERITONEAL MACROPHAGES

摘要: 异唑类衍生物来氟米特(leflunomide)是一种新型抗炎及免疫调节剂。本文首次发现脂质类炎症介质血小板激活因子(PAF)可显著诱导体外培养的兔滑膜细胞DNA合成。来氟米特及其主要代谢产物A771726在0.1～10μmol·L^-1范围内呈剂量依赖性地抑制PAF诱导滑膜细胞DNA合成。对于钙离子载体A23187诱导的大鼠腹腔巨噬细胞释放PAF,来氟米特和A771726亦呈时间和剂量依赖性的抑制作用。来氟米特在PAF生成和作用两个环节上都呈现出显著的抑制作用。

Abstract: eflunomide(LFM ,HWA486)isanisoxazolderivativewithantiphogisticandnovel immunomodulating properties.It has been shown to be very effective in preventing and curingarthritis.In this report we found that platelet-activating factor(PAF)at 0. 1～10μg· mL^-1 signifi-cantly stimulated DNA synthesis in cultured rabbit synovial cells. While LFM and its metaboliteA771726 elicited inhibitory effects on this action of PAF. These two agents were also shown tomarkedly inhibit A 2318 7 induced PAF production from rat peritoneal macrophages. The inhibitionwas dose and time-dependent.The inhibitory effects of LFM and A77l726 on DNA synthesis insynovial cells and PAF production from macrophages may play an important role in the anti-inflammatorv effects of LFM.