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 (lipopolysac-charide, 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 poly-merase 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 phosphoryl-ation, down - regulating the expression of c - jun and c - fos, and restraining downstream inflammatory factors TNF - α release.%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.
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