【摘要】 目的探讨脂氧素A4 (LXA4 )对皮肤炎症与增殖反应的作用及其机制。方法应用欧亚瑞香脂制备小鼠的外耳炎症与增殖反应模型,应用LXA4 ( 1∶10nmol/L)局部注射每4h 1次,对部分小鼠静脉注射伊文思蓝或[3H] 胸腺嘧啶。2 4h后测定外耳湿重(反映水肿)、伊文思蓝比色(反映血管通透性)、弹性硬蛋白酶活性(反映中性粒细胞浸润)、白介素 8(IL 8)蛋白与基因表达、核因子 κB(NF κB)活化。72h后测定[3H] 胸腺嘧啶掺入量。结果在欧亚瑞香脂模型耳,2 4h后外耳湿重、伊文思蓝比色、弹性硬蛋白酶活性、IL 8蛋白与基因表达、NF κB活化均升高。LXA4 治疗2 4h后呈剂量依赖性地抑制这些参数的升高。在72h后,外耳组织的[3H] 胸腺嘧啶掺入量升高,LXA4 治疗后呈剂量依赖性地抑制其升高。结论LXA4 可抑制欧亚瑞香脂所致的外耳炎性与增殖反应,其机制与抑制浸润中性粒细胞的NF κB活化与IL 8合成有关。更多还原

【Abstract】 Objective To explore the mechanisms by which lipoxin A₄（LXA₄） inhibits dermal inflammation and hyperplasia induced by mezerein. Methods The ear inflammatory model was induced by topical injection of mezerein. LXA₄ at the dose of 1 to 10 nmol/L was applied topically to the mouse ears by injection every 4 h until 72 h after injection of mezerein. Evans blue or -thymidine was injected intravenously after induction of the model in some mice. Ear weight was served as a criterion for edema of tissue at 24 h following injection of mezerein. Colorimetric assay of Evans blue was performed for evaluation of vascular permeability. Elastase activity was measured spectrophotometrically for evaluation of neutrophil infiltration. Interleukin-8 （IL-8） protein of tissue was determined by ELISA and the mRNA expression was assessed by RT-PCR. DNA binding activity of nuclear factor-κB （NF-κB） was analyzed by electrophoretic mobility shift assay. -thymidine incorporation was assessed for evaluation of dermal hyperplasia at 72 h after injection of mezerein. Results Treatment of mouse ear with LXA₄ exhibited a dose-dependent inhibitory effects on edema, neutrophil infiltration, vascular permeability, expressions of IL-8 protein and mRNA, NF-κB activity at 24 h and on dermal hyperplasia at 72 h following induction of the ear model induced by mezerein. Conclusion LXA₄ displays a topical anti-inflammatory and anti-proliferative role on ear model of mice induced by mezerein and these effects were related with down-regulation of NF-κB activity and IL-8 expression by LXA₄.更多还原