P物质通过MAPKs信号通路缓解早产大鼠高氧肺损伤  

Relieving effect of substance P on hyperoxia-induced lung injury in premature rats via MAPKs signaling pathway

作　　者：田名洋 李青[2] 郑兴惠[2] 毕云霞[2] 许峰[3] 黄波[2] 

机构地区：[1]遵义医学院研究生院,贵州遵义563000 [2]遵义市第一人民医院儿科,贵州遵义563000 [3]重庆医科大学附属儿童医院儿童重症医学科,重庆400014

出　　处：《基础医学与临床》2016年第3期358-363,共6页Basic and Clinical Medicine

基　　金：贵州省科学技术基金(黔科合J字【2011】2341号);贵州省卫生厅科学技术基金(qzwkj2011-1-092);遵义市科学技术局科技项目【遵市科合社志(2011)22号)】

摘　　要：目的探索神经肽P物质(SP)对高氧暴露早产鼠肺组织的作用及与丝裂原活化蛋白激酶家族(MAPKs)信号传导机制的关系。方法将早产鼠随机分为常氧组、常氧+SP干预组、高氧组和高氧+SP干预组;实验第3、7及14天时,观察肺组织病理改变;测肺湿/干重;放免法测肺组织中SP的含量;分别采用硫代巴比妥酸法、亚硝酸盐法和二硝基苯甲酸法检测丙二醛(MDA)、过氧化物歧化酶(SOD)和谷胱甘肽-过氧化物酶(GSH-Px)水平;TUNEL法检测肺组织凋亡细胞;Western blot法检测MAPKs蛋白含量。结果高氧暴露后肺组织损伤,湿/干重增加,SP含量降低,MDA含量增加SOD和GSH-Px含量降低(P<0.05),凋亡细胞增多,并随着高氧暴露时间延长改变越明显,SP干预后肺损伤有所改善,湿/干重回降,MDA含量降低,SOD、GSH-Px含量增加(P<0.05),TUNEL阳性细胞减少;高氧组细胞外信号调节蛋白激酶(ERK)、c-Jun氨基末端激酶(JNK)及P38激酶(P38)蛋白表达明显高于空气组(P<0.05),且随时间的延长变化增大,而SP干预后ERK蛋白表达越加增强(P<0.05),JNK、P38蛋白表达明显减弱(P<0.05)。结论高氧可引起早产鼠肺组织氧化损伤;SP可通过干预MAPKs的表达从而保护氧化应激状态下肺组织。Objective To explore the impact of exposure to hyperoxia on lung tissue from premature rats. Methods Sixty premature Wistar rats were divided randomly into 4 groups ： normoxic group, normoxic ＋ SP group, hyperoxic group, hyperoxic ＋ SP group. Each group was divided into 3 subgroups according to the 3 time points of 3 d, 7 d and 14 d. Lung pathology, wet/dry （W/D） ratio of lung tissue and content of SP in lung were evaluated. MDA, SOD and GSH-Px were detected. Cell apoptosis was detected by TUNEL. MAPKs was detected by Western blot. Results The rats in hyperoxia groups had lung injury, and it was increased dependently with the time of exposureto hyperoxia, while treated with substance P the injury was alleviated. The W/D ratio of rats in hyperoxia group significantly increased （ P 〈 0.05 ）, while in substance P group W/D ratio decreased （ P 〈 0.05 ）. The content of SP in hyperoxia group reduced and the content of SP decreased（ P 〈0.05 ）. The vitality of MDA in the hyperoxia group increased significantly, and the vitality of hyperoxia ＋ SP group decreased （ P 〈 0. 05 ）. The vitality of SOD, GSH-Px in the hyperoxia group decreased （ P 〈 0.05 ）, the vitality of SOD, GSH-Px increased in substance P group （P 〈 0.05 ）. TUNEL-positive cell of hyperoxia groups significantly increased. TUNEL-positive cell de- creased in substance P group. The expression of p-JNK, P38 and ERK protein was higher in the hyperoxia group than that in the normoxic group（ P 〈 0.05 ）, and the expression of p-JNK, P38 and ERK protein increased in time dependently. However, the expression of p-JNK and P38 protein was inhibited in hyperoxia ＋ SP group （ P 〈 0.05 ）. The expression of ERK protein increased in hyperoxia ＋ SP group （ P 〈 0. 05 ）. Conclusions Hyperoxia leads to lung injury in premature rats and treatment with SP may protect lung injury in oxidative stress condition through inhibiting MAPKs pathway.

关 键 词：神经肽P物质 高氧 肺损伤 MAPKS 

分 类 号：R563.8[医药卫生—呼吸系统]