木酚素二硫戊环类似物抑制γ-干扰素和脂多糖rn在巨噬细胞中诱生一氧化氮

摘要

AIM: To investigate the effect of a group of novel synthetic dithiolane analogs of lignans and a well characterized platelet-activating factor (PAF) receptor antagonist,L659,989 on PAF-receptor binding, IFN-γ-and lipopolysaccharide (LPS)-induced NO production, and steady-state inducible nitric-oxide synthase (iNOS)mRNA expression. METHODS: PAF-receptor binding study was performed by displacement of 3H-PAF from rabbit platelet membrane; NO production was quantitated by measuring the NO oxidation product, nitrite, in conditioned culture medium; expression of iNOS mRNA was assessed by Northern blot analysis. RESULTS: The dithiolane analogs inhibited the production of NO, decreased iNOS mRNA expression and antagonized PAF-receptor binding. L659,989 had no effect on NO production and iNOS mRNA expression. Among the compounds tested, there was no simple correlation between their PAF-receptor antagonistic and iNOS inhibitory activities. CONCLUSION: The dithiolane analogs are a new synthetic chemical class of iNOS expression regulators with dual biologic functions: inhibiting iNOS induction and blocking PAF-receptor.%研究木酚素二硫戊环类似物及血小板活化因子(PAF)受体拮抗剂L-659，989对PAF-受体结合，对γ-干扰素和脂多糖诱导的一氧化氮(NO)生成，以及对iNOS mRNA表达的影响.方法：通过对兔血小板膜中3H标记的PAF-受体竞争结合试验来研究对PAF-受体的拮抗作用；测定NO的氧化产物亚硝酸盐来定量NO的生成.用RNA印迹分析来研究对i-NOS mRNA表达的影响.结果：二硫戊环类似物抑制NO的生成，减少iNOS mRNA的表达，拮抗3H-PAF受体.L-659，989对NO生成和iNOS mRNA表达没有影响.受试物的PAF受体拮抗活性和iNOS抑制活性之间无简单关联.结论：木酚素二硫戊环类似物是iNOS表达的新型调控剂，具有抑制iNOS诱导和拮抗PAF受体的双重活性.