槐定碱对内毒素肺损伤小鼠p38MAPK的影响

Effect of Sophoridine on the Expression of p38 Mitogen-activated Protein Kinase in Acute Lung Injury Mice Induced by LPS

目的探讨内毒素(细菌脂多糖,LPS)肺损伤小鼠肺组织p38丝裂原活化蛋白激酶(p38MAPK)表达的变化以及槐定碱对其影响。方法 60只BALB/c小鼠,除正常对照组、槐定碱对照组外,内毒素肺损伤模型组(LPS模型组)、槐定碱治疗高(12mg.kg-1)、中(6mg.kg-1)、低(3mg.kg-1)剂量组的BALB/c小鼠均尾静脉注射LPS制备急性肺损伤模型,注射后30min再分别腹腔注射生理盐水或槐定碱12、6、3mg.kg-1,各组均处理后6h取材,肉眼及光镜观察肺组织的病理变化,免疫组化SP法检测肺组织中总p38、磷酸化p38的表达,硝酸还原酶法检测血清NO含量。结果 LPS模型组肺脏病理改变明显加重,肺组织总P38和磷酸化p38的表达均增多和增强(P<0.01);血清NO显著升高(P<0.01);槐定碱三个剂量治疗组病理损伤均不同程度改善,总P38表达与LPS组比较差异无统计学意义,但磷酸化p38表达均显著小于模型组(P<0.01),血清NO含量显著低于LPS模型组(P<0.01)。结论 p38MAPK参与了内毒素肺损伤的发病过程,槐定碱的抗内毒素肺损伤机制可能与下调p38MAPK的表达,抑制NO的释放有关。

Objective To explore the effect of Sophoridine on the expression of p38 mitogen-activated protein kinase（p38MAPK） in lung injury mice induced by endotoxin（I.e.lipopolysaccharide,LPS）.Methods Sixty BALB/c mice were randomly divided into six groups.The lung injury model group and the Sophoridine treatment group were injected LPS（7mg·kg-1,E.coli O55：B5） by vena caudalis 30 minutes after the Sophoridine（12mg·kg-1,6 mg·kg-1,3 mg·kg-1））was injected via peritoneal cavity respectively.Pathological changes of lung tissues were observed.The protein expression of total p38 and phospho-p38 were examined by immunohistochemistry SP method and serum NO level measured by nitrate reductase method.Results In LPS-induced lung injury model group the lung tissue pathological changes were aggravated.The total p38 and phospho-p38 positive cells and positive signals in LPS-induced lung injury model group were significantly higher than those in the normal control group（P〈0.01）with immunohistochemical detection.The levels of serum NO increased in LPS-induced lung injury model group.Sophoridine could relieve pathological histological changes of lung tissue.Positive cells and positive signal intensity of phosphor-p38 in three treatment group were less than those in the model group（P〈0.01）,and the levels of serum NO in three treatment group were significantly decreased.Conclusion p38MAPK may play an active role in pathological process of LPS-induced acute lung injury.The mechanism of Sophoridine anti-endotoxin lung injury have strong relationship with inhibiting p38 phosphorylation and restraining downstream inflammatory factors NO release.