糖皮质激素对高氧诱导新生大鼠肺组织RAGE-NF-κB通路的影响  

Effects of glucocorticoid on RAGE-NF-κB pathway in hyperoxia-induced lung tissues of neonatal rats

作　　者：胡剑[1] 俞敏[1] 唐云[1] 田兆方[1] 

机构地区：[1]南京医科大学附属淮安第一医院新生儿科,江苏淮安223300

出　　处：《中国当代儿科杂志》2015年第1期81-85,共5页Chinese Journal of Contemporary Pediatrics

基　　金：江苏省临床医学专项(BL2014063)

摘　　要：目的探讨RAGE-NF-κB信号通路在新生大鼠高氧肺损伤过程中的变化,以及糖皮质激素对其的影响。方法 24只新生大鼠随机分为空气对照组、高氧模型组和激素干预组。模型组新生大鼠于生后即暴露于95%氧气浓度环境中1周,空气对照组大鼠生后仅暴露于同室内空气中饲养7 d,激素干预组于造模后行尾静脉注射地塞米松(1 mg/kg),隔天1次,共3次。日龄13 d时处死全部大鼠,RT-PCR检测各组肺组织RAGE m RNA及NF-κB m RNA的表达;Western blot检测RAGE及NF-κB蛋白水平;ELISA法检测血清及肺泡灌洗液(BALF)中TNF-α和s RAGE含量;苏木精-伊红染色后行肺组织病理学评估。结果与对照组和激素干预组相比,高氧模型组肺组织RAGE、NF-κB的m RNA和蛋白表达水平均明显增高(均P<0.05),血清中s RAGE含量明显升高(P<0.01),BALF中s RAGE含量下降(P<0.01);与对照组相比,激素干预组肺组织RAGE、NF-κB的m RNA和蛋白表达水平明显升高(P<0.05),血清中s RAGE含量明显升高(P<0.05),而BALF中s RAGE含量明显下降(P<0.05)。结论 RAGE-NF-κB通路在高氧诱导的新生大鼠肺损伤中活化增强,糖皮质激素可能通过下调RAGE-NF-κB信号通路对高氧肺损伤发挥保护作用。Objective To explore the change of RAGE-NF-κB signaling pathway during the course of hyperoxia-induced lung injury in newborn rats, and the effect of glucocorticoid on this pathway. Methods Twenty-four Sprague-Dawley neonatal rats were randomly divided into three groups （n=8 each）：sham control （control group）, hyperoxia-induced acute lung injury （model group） and glucocorticoid-treated acute lung injury （glucocorticoid group）. Rats were sacriifced at 13 days after birth. RAGE and NF-κB expression levels in lung tissues were detected by reverse transcription polymerase chain reaction, Western blot and immunohistochemistry analysis. The levels of tumor necrosis factorα（TNF-α） and sRAGE in bronchoalveolar lavage lfuid （BALF） and serum were measured using ELISA. Lung damage was evaluated by histological examinations. Results RAGE and NF-κB mRNA and protein expression levels in lung tissues were signiifcantly increased in the model and glucocorticoid groups compared with the control group （P〈0.05）. Serum RAGE concentrations were signiifcantly increased but RAGE concentrations in BALF were signiifcantly reduced in the model and glucocorticoid groups compared with the control group （P〈0.05）. RAGE and NF-κB expression at both mRNA and protein levels in lung tissues was signiifcantly lower in the glucocorticoid group than in the model group （P〈0.05）. RAGE concentrations were signiifcantly lower in serum （P〈0.05）, but were higher in BALF （P〈0.05） in the glucocorticoid group than in the model group. Conclusions RAGE-NF-κB pathway plays an important role in hyperoxia-induced lung injury in neonatal rats, and glucocorticoid administration may play a protective role against the lung injury by down-regulating RAGE-NF-κB signaling pathway.

关 键 词：糖皮质激素 晚期糖基化终末产物受体 肺损伤 新生大鼠 

分 类 号：R722.1[医药卫生—儿科]