摘要
目的研究肺表面活性物质(pulmonary surfactant,PS)对脂多糖(lipopolysaccharides,LPS)诱导的急性肺损伤(acutelung injury,ALI)小鼠的肺保护作用及相关机制。方法气管内雾化LPS建立ALI小鼠模型,PS于LPS建模前0.5 h经小鼠气管内雾化提前给药干预。气管内雾化LPS 2 h后处死小鼠,肺组织行HE染色及病理评分,qRT-PCR检测肺组织TNF-α和IL-1βmRNA转录水平,ELISA检测肺组织匀浆中TNF-α和IL-1β浓度,Western blot检测肺组织IκB-α、NF-κB、P38MAPK、ERK1/2和JNK蛋白表达及磷酸化水平。结果 PS干预可以明显减轻ALI小鼠肺组织病理损伤及评分(P<0.05),显著降低ALI小鼠肺组织TNF-α、IL-1βmRNA转录水平(P<0.05)和肺组织匀浆中TNF-α、IL-1β质量浓度(P<0.05),明显抑制ALI小鼠肺组织IκB-α、NF-κB和P38MAPK蛋白磷酸化水平(P<0.05)。结论外源性PS可通过抑制LPS诱导的炎症信号级联传导,进而抑制NF-κB信号环路的正反馈性放大,下调炎症介质表达,从而减轻肺组织病理损伤。
The present study was performed to investigate the protective effects and mechanisms of pulmonary surfactant （PS） on lipopolysaccharides （LPS） induced acute lung injury （ALI） in mice. ALI was induced in mice by intratracheally atomization of LPS, while PS intervene was carried out intratracheally at 0.5 hours before. Two hours after LPS administration, the animals in each group were sacrificed. Then pulmonary histological changes were evaluated by hematoxylin-eosin stain; transcription level of TNF-α and IL-β mRNA in lung tissue were detected by qRT-PCR; concentration of TNF-α and IL-1β in lung tissue homogenates were measured by ELISA; and phosphorylation of IKB-alpha, NF-kappa B, P38MAPK, ERK1/2 and JNK in lung tissue were determined by Western blotting. We found that PS pretreatment markedly attenuated lung histopathological change and score （P〈 0.05）. And the transcription level of TNF-α and IL-1β mRNA in lung tissue were also reduced by PS （P〈 0.05）. In addition, PS inhibited concentration of TNF-α and IL-1β in lung tissue after LPS challenge （P〈 0.05）. Moreover, PS obviously restrained LPS-induced activation of IKB-alpha, NF-kappa B and P38MAPK （P〈 0.05）. In conclusion, all the result indicated that exogenous PS can attenuates LPS-induced acute lung injury by inhibiting signal transduction and block positive feedback loop of NF-kappa B.
出处
《免疫学杂志》
CAS
CSCD
北大核心
2013年第7期583-587,共5页
Immunological Journal
基金
国家自然科学基金面上项目(81070003)
广东省科技计划项目(2011B031800170)
