15d-PGJ_(2)抑制LPS对巨噬细胞的毒性作用

15d-PGJ_(2)Inhibits the Toxicity of LPS to Macrophages

目的探讨15脱氧前列腺素J2(15dPGJ2)作用下脂多糖(lipopolysaccharide,LPS)对巨噬细胞毒性作用的影响。方法体外培养Wistar大鼠腹腔巨噬细胞,加入LPS(终浓度为10μg/ml)的同时加入终浓度为2μg/ml的15dPGJ2,用MTT法检测巨噬细胞活力;用硝酸还原酶法测一氧化氮(NO)的浓度。结果巨噬细胞经LPS(10μg/ml)处理后,于24h开始MTT值明显下降,与对照组、15dPGJ2组相比,差异有显著性(P<0.05),LPS+15dPGJ2组与其他3组相比,MTT值在48h后表现出显著性差异(P<0.05),LPS组NO在前24h内释放明显增多,高于对照组、15dPGJ2组和LPS+15dPGJ2组(P<0.05),24h后NO释放减少。LPS+15dPGJ2组NO的释放在24h后均高于对照组和15dPGJ2组,差异有显著性(P<0.05)。结论15dPGJ2能部分拮抗10μg/mlLPS对巨噬细胞的毒性作用,可能与NO的产生有关。提示15dPGJ2可作为维持巨噬细胞活性药物,以防止内毒素诱导的免疫损伤。

Objective To investigate the effects of 15-deoxy -12,14-prostaglandin J_2 (15d-PGJ_2) on the toxicity of lipopolysaccharide to rat peritoneal macrophages.Methods Macrophages in vitro cultured were isolated from the peritoneum of wistar rats and treated with LPS(final concentration,10 μg/ml),together with or without 15d-PGJ_2 at the final concentration of 2 μg/ml.Cell viability was evaluated by MTT. The production of nitric oxide(NO) was determined by nitrate reductase method. Results The MTT values in LPS groups were significantly reduced(P<0.05) after 24h,compared with the controls and the groups only with 15d-PGJ_2. There was significant difference between LPS and LPS+15d-PGJ_2 groups(P<0.05) after 48h.The production of NO in LPS group was increased significantly(P<0.05) compared with other groups at the first 24 h,but reduced afterward. Remarked increase was observed in LPS+15d-PGJ_2 groups compared with the controls and in the groups only with 15d-PGJ_2 in the production of NO(P<0.05) after 24 h.Conclusion 15d-PGJ_2 could partially antagonize the toxicity of LPS(10 μg/ml) to rat peritoneal macrophages which might contribute to its inhibition of production of NO.These data suggest that 15d-PGJ_2 might be taken as an agent for maintaining the viability of macrophages and reduce LPS-induced immunologic damage.