摘要
目的探讨c-Jun氨基末端激酶(JNK)信号转导通路在高体积分数氧(高氧)诱导的肺损伤大鼠中的作用。方法24只3周龄Wistar大鼠随机分为3组(n=8):空气对照组、高氧暴露7d组、高氧暴露7d+JNK抑制剂干预组。高氧暴露组置于吸氧体积分数(FiO2)≥950mL.L-1常压高氧仓中,空气对照组置于同室常压空气中(FiO2=210mL.L-1),JNK抑制剂干预组动物经腹腔注射SP60012530mg·kg-1,2h后再予高氧暴露。光镜下观察各组肺组织病理学改变,并测定肺湿质量/干质量(W/D)、支气管肺泡灌洗液(BALF)蛋白水平和肺通透指数,末端标记法分析肺组织细胞凋亡的变化,蛋白免疫印迹法检测肺组织磷酸化-JNK(p-JNK)蛋白水平。结果与空气对照组比较,高氧暴露7d组肺组织出现明显充血、水肿、出血及大量炎性细胞浸润,肺W/D、BALF蛋白水平、肺通透指数及肺组织细胞凋亡指数和p-JNK蛋白水平均显著增加(Pa<0.05)。凋亡细胞主要见于小呼吸道和肺泡上皮细胞及血管内皮细胞。高氧暴露7d+JNK抑制剂干预组较高氧暴露7d组肺组织病理损伤及炎性渗出、水肿明显减轻,肺W/D、BALF蛋白水平、肺通透指数及肺组织细胞凋亡指数和p-JNK蛋白水平均显著减少(Pa<0.05)。结论JNK信号转导通路在高氧肺损伤中被激活,可能发挥促炎症和细胞凋亡效应,阻断或抑制JNK信号通路,对高氧肺损伤大鼠可能起保护作用。
Objective To explore the effect of c-Jun NH2-terminal kinase（JNK）signal transduction pathway on hyperoxia-induced lung injury in rats.Methods Twenty-four Wistar rats aged 3 weeks were randomly divided into 3 groups（n=8）：room-air control group,7 d hyperoxia exposure group,and 7 d hyperoxia exposure with inhibitor of JNK intervention group.The rats in hyperoxia exposure group were exposed to high concentration of oxygen [fractional concentration of inspired oxygen（FiO2）≥950 mL·L^-1] at normal pressure.The rats in room-air control group were placed in room air（FiO2=210 mL·L^-1）at normal pressure.The rats in JNK inhibitor intervention group were intraperitoneally injected 30 mg·kg^-1 SP600125 and exposed to hyperoxia 2 h later.The histopathological changes of lung tissues were observed by means of light microscope,therefore the changes of lung W/D weight ratio,total protein in bronchoalveolar lavage fluid（BALF）and lung permeation index were detected.The extent of lung cells apoptosis was analyzed by terminal deoxynucleotidyltrans-ferase-mediated dUTP nick end labeling assay.The protein level of p-JNK was measured by Western blotting analysis.Results Compared with room-air control group,conspicuous hyperaemia,edema,hemorrhage and extensive inflammation cells infiltration in the lung tissues were significantly observed in 7 d hyperoxia exposure group.The lung W/D weight ratio,total protein in BALF,lung permeation index,cell apoptotic index and the p-JNK protein levels of lung tissues all significantly increased in 7 d hyperoxia exposure group compared with those in room-air control group（Pa0.05）.The apoptosis cells were evident in alveolar epithelial cells,distal bronchiolar epithelium and endothelial cells.The histopathological injury of lung tissues,inflammatory effusion,edema were significantly decreased,and the lung W/D weight ratio,total protein in BALF,lung permeation index,cell apoptotic index and the p-JNK protein levels of lung tissues all reduced markedly in 7 d hyperoxia exposure with inhibitor of JNK intervention group compared with those in 7 d hyperoxia exposure group（Pa0.05）.Conclusions The activation of JNK signal transduction pathways may initiate under hyperoxia stress and may play a role in promoting inflammation and cells apoptosis in hyperoxia-induced lung injury.Inhibition of JNK signal transduction pathway may be protective for hyperoxia-induced lung injury.
出处
《实用儿科临床杂志》
CAS
CSCD
北大核心
2010年第6期394-397,共4页
Journal of Applied Clinical Pediatrics
基金
国家自然科学基金(30370618)
作者简介
胡兰，女，主治医师，讲师，硕士学位，研究方向为肺损伤。
