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(1nmol/L,10nmol/L)局部注射,4h1次,对部分小鼠静脉注射伊文思蓝或[3H]胸腺嘧啶。24h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(IL8)蛋白与基因表达、核因子κB(NFκB)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,24h后外耳湿重、伊文思蓝比色、弹性硬蛋白酶活性、IL8蛋白与基因表达、NFκB活化均升高。LXA4治疗24h后抑制这些参数的升高;72h后,外耳组织的[3H]胸腺嘧啶掺入量升高,LXA4治疗后可抑制其升高。结论LXA4可抑制欧亚瑞香脂所致的外耳炎症与增殖反应,其机制与抑制浸润中性粒细胞的NFκB活化与IL8合成有关。
Objective To identify the inhibitory effect of lipoxin A_4(LXA_4) on dermal inflammation and hyperplasia induced by mezerein,and to explore the mechanisms of LXA_4 actions.Methods The ear inflammatory model was induced by topical injection of mezerein.LXA_4 at the dose of 1nM or 10 nmol/L was applied to the mouse ears by injection every 4 hours until 72 hours after injection of mezerein.Evans blue or [~3H]-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 hours 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.[~3H]-thymidine incorporation was assessed for evaluation of dermal hyperplasia at 72 hours after injection of mezerein.Results Treatment of mouse ear with LXA_4 exhibited the inhibitory effects on edema,neutrophil infiltration,vascular permeability,expressions of IL-8 protein and mRNA,NF-κB activity at 24 hours and on dermal hyperplasia at 72 hours following induction of the ear model induced by mezerein.Conclusion LXA_4 displays the 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 LXA_4.
出处
《中国皮肤性病学杂志》
CAS
北大核心
2005年第7期391-394,共4页
The Chinese Journal of Dermatovenereology
基金
江苏省135医学重点人才工程资助(2002-45)
