苦参碱对博莱霉素诱导的肺纤维化大鼠中Nrf2表达的影响

目的观察Nrf2在博莱霉素诱导的大鼠肺纤维化中的表达及作用,以及苦参碱干预对大鼠肺组织中Nrf2表达的影响。方法按随机数字表法将120只SD大鼠分为正常空白对照组(C)、模型组(M)、泼尼松处理组(P)、苦参碱50处理组(M50)、苦参碱100处理组(M100)。采用免疫组化法(SP)分析每组不同时间点肺组织中Nrf2蛋白水平,RT-PCR检测大鼠肺组织中Nrf2 m-RNA的表达。结果四组实验组动物肺系数在造模后第7、14、28天均高于空白对照组动物(P<0.05);M100组动物肺系数明显低于M组及P组、M50组动物(P<0.05);图像定量分析显示Nrf2在M组、P组、M50组和M100组造模后Nrf2表达高于C组,其中M组的表达量低于P组、M50组、M100组,且其表达在第7、14和28天依次降低(P<0.05)。结论 Nrf2表达在博来霉素诱导的大鼠肺间质纤维化有一定抑制作用,其机制之一可能与早期抑制氧化应激反应有关;苦参碱有抑制博来霉素诱导的大鼠肺纤维化作用,可能与早期上调Nrf2表达调节氧化应激有关。

Effects of matrine on expression of Nrf2 in bleomycininduced pulmonary fibrosis in rats

【Objective】 To observe the role and expression of Nrf2 with or without matrine intervention in pulmonary fibrosis induced by the bleomycin in rats.【Method】 120 SD rats were divided into normal control group(C),model group(M),prednisone treatment group(P),matrine 50 treatment group(M50),matrine 100 treatment group(M100) with the random number table.Nrf2 protein level at different time in each group was analyzed by immunohistochemistry(SP),and the Nrf2 mRNA level was detected by RT-PCR.【Result】 The animal lung coefficient in the four experimental groups were higher than control animals in 7,14,28 d after modeling(P <0.05),and in the M100 group,it was significantly lower than the M group,P group and M50 grou(P <0.05);Quantity of Nrf2 expressed in M group,the P group,the M50 group and M100 group was higher than that in C group,while in group M,it was not only lower than group P,group M50 and group M100,but its expression was in turn lower in 7 d,14 d and 28 d(P <0.05) with image quantitative analysis.【Conclusion】 Nrf2 expression can control the interstitial pulmonary fibrosis induced by bleomycin in rats in some degree,and one of the mechanisms may be associated with early inhibition of oxidative stress response.Matrine can control the interstitial pulmonary fibrosis induced by bleomycin in rats may be associated with oxidative stress regulated by the expression of Nrf2 at early stage.