槐定碱对内毒素血症小鼠肺组织p38MAPK/AP-1表达的影响  

Effects of Sophoridine on p38 MAPK/AP-1 Signaling Pathwaysin Mouse with Endotoxemia

作　　者：梁锦屏[1] 韩怀钦[1] 周娅[1] 

机构地区：[1]宁夏医科大学基础医学院病原生物学与免疫学系,银川750004

出　　处：《宁夏医科大学学报》2012年第12期1239-1242,共4页Journal of Ningxia Medical University

基　　金：国家自然科学基金(30660227);教育部新世纪优秀人才支持计划(NCET-06-0916);宁夏卫生厅重点科研计划(2011032);宁夏医科大学面上项目(XM201005)

摘　　要：目的观察槐定碱对内毒素血症小鼠p38MAPK信号分子、转录因子激活蛋白1(AP-1)及下游炎症因子TNF-α影响,探讨槐定碱抗内毒素的药理机制。方法 BALB/c小鼠尾静脉注射LPS(7mg.kg-1)制备内毒素血症小鼠模型,30min后腹腔注射槐定碱,剂量分别为12、6和3mg.kg-1,6h后取血和肺组织。免疫印迹法(Western-blot)检测肺组织总p38MAPK、磷酸化p38 MAPK蛋白表达,RT-PCR检测肺组织c-jun和c-fos mRNA表达,放免法检测血清中TNF-α含量。结果与内毒素血症模型组比较,三个剂量槐定碱干预组肺组织中磷酸化p38蛋白表达显著降低(P<0.01或P<0.05),c-jun和c-fos mRNA表达显著减少(P<0.01或P<0.05),血清中TNF-α含量明显下降(P<0.01或P<0.05)。结论槐定碱可抑制肺组织中p38MAPK的磷酸化,下调c-jun和c-fos mRNA的表达,抑制下游炎症因子TNF-α表达。Objective To explore the effect and the possible mechanism of Sophoridine on p38 mitogen-activated protein kinase（p38MAPK）,activating protein-1 and TNF-α in mouse with endotoxin（lipopolysaccharide,LPS）.Methods The endotoxemia mouse models were induced by vena caudalis injection of LPS（7mg·kg-1,E.coli O55：B5） and,the Sophoridine（12,6,3 mg·kg-1）was injected via peritoneal cavity respectively 30 min later.The protein expression of total p38 and phospho-p38 were examined by Western blotting.C-jun and c-fos mRNA expression of lung tissue was measured by the reverse transcription polymerase chain reaction（RT-PCR）,and serum TNF-α level was detected by radioimmunoassay.Results Compared with LPS model group,protein expression of phospho-p38 of the lung,and mRNA expression of c-jun and c-fos of the lung was significantly reduced in the Sophoridine 3 dose intervention groups（P〈0.01 or P〈0.05） and the levels of serum TNF-α were significantly reduced（P〈0.01）.Conclusion The mechanism of Sophoridine anti-endotoxin lung injury have strong relationship with inhibiting p38 phosphorylation,down-regulating the expression of c-jun and c-fos,and restraining downstream inflammatory factors TNF-α release.

关 键 词：槐定碱 内毒素 P38MAPK C-JUN C-FOS 

分 类 号：R285.5[医药卫生—中药学]