复痿膏对特发性肺纤维化大鼠FGF/ERK通路的影响

Effects of Fuwei ointment on FGF/ERK pathway of idiopathic pulmonary fibrosis rats

目的探讨复痿膏对特发性肺纤维化大鼠成纤维细胞生长因子(FGF)/细胞外信号调节蛋白激酶(ERK)通路因子FGF1、FGF2、成纤维细胞生长因子受体1(FGFR1)、FGFR2、ERK1、ERK2 mRNA表达的影响。方法将健康雄性SD大鼠随机分为空白组、模型组、泼尼松组、复痿膏组、复痿膏+泼尼松组,每组30只。除空白组外,其余组大鼠均进行特发性肺纤维化造模。造模第2天起,泼尼松组给予泼尼松6.25 mg/kg灌胃,复痿膏组给予复痿膏10.80 g生药/kg灌胃,复痿膏+泼尼松组给予泼尼松6.25 mg/kg和复痿膏10.80 g生药/kg灌胃。每组分别于灌胃7 d、14 d、28 d后各处死10只大鼠提取肺组织,实时定量PCR方法检测各组大鼠肺组织中FGF1、FGF2、FGFR1、FGFR2、ERK1、ERK2 mRNA表达水平;HE染色和Masson染色观察灌胃7 d后各组大鼠肺组织病理学变化。结果灌胃7 d、14 d、28 d后,模型组大鼠肺组织中FGF1、FGF2、FGFR1、FGFR2、ERK1、ERK2 mRNA表达水平均明显高于同期空白组(P均<0.05),泼尼松组、复痿膏组和复痿膏+泼尼松组大鼠肺组织中FGF1、FGF2、FGFR1、FGFR2、ERK1、ERK2 mRNA表达水平均明显低于同期模型组(P均<0.05),复痿膏+泼尼松组均明显低于同期泼尼松组和复痿膏组(P均<0.05),泼尼松组均明显低于同期复痿膏组(P均<0.05)。病理结果显示泼尼松组、复痿膏组和复痿膏+泼尼松组大鼠肺纤维化和肺泡炎均有改善,复痿膏+泼尼松组改善更显著。结论复痿膏可降低特发性肺纤维化大鼠肺组织中FGF1、FGF2、FGFR1、FGFR2、ERK1、ERK2 mRNA表达水平,减轻大鼠肺纤维化程度,但单用效果不如泼尼松,与泼尼松联合应用效果更好。

Objective It is to investigate the effect of Fuwei ointment on the mRNA level of fibroblast growth factor(FGF)/extracellular signal-regulated protein kinase(ERK)pathway factors FGF1,FGF2,fibroblast growth factor receptor 1(FGFR1),FGFR2,ERK1,ERK2 in rats with idiopathic pulmonary fibrosis.Methods Healthy male SD rats were randomly divided into blank group,model group,prednisone group,Fuwei ointment group,Fuwei ointment+prednisone group,30 rats in each group.Except for the blank group,the rats in the other groups were modeled with idiopathic pulmonary fibrosis.From the second day of modeling,the prednisone group was given prednisone 6.25 mg/kg by gavage,the Fuwei ointment group was given Fuwei ointment 10.80 g crude drug/kg,and the Fuwei ointment+prednisone group was given prednisone 6.25 mg/kg and Hefuwei ointment 10.80 g crude drug/kg by gavage.The lung tissues were extracted from 10 rats in each group at 7 days,14 days,and 28 days after gavage.Real-time quantitative PCR was used to detect the expression levels of FGF1,FGF2,FGFR1,FGFR2,ERK1,ERK2 mRNA in the lung tissues of rats in each group;HE staining and Masson staining were used to observe the pathological changes of the lung tissues of rats in each group at 7 days after intragastric administration.Results After gavage for 7 days,14 days,and 28 days,the expression levels of FGF1,FGF2,FGFR1,FGFR2,ERK1,and ERK2 mRNA in the lung tissue of the model group were significantly higher than those of the blank group during the same period(all P<0.05).The expression levels of FGF1,FGF2,FGFR1,FGFR2,ERK1 and ERK2 mRNA in the lung tissue of rats in the Fuwei ointment group and Fuwei ointment+prednisone group were significantly lower than those of the model group at the same time(all P<0.05),Fuwei ointment+prednisone group was significantly lower than the prednisone group and Fuwei ointment group at the same period(all P<0.05),and the prednisone group was significantly lower than the Fuwei ointment group at the same period(P<0.05).Pathological results showed that the pulmonary fibrosis and alveolitis in the prednisone group,the Fuwei ointment group and the Fuwei ointment+prednisone group were all improved,and the improvement was more significant in the Fuwei ointment+prednisone group.Conclusion Fuwei ointment can reduce the expression level of FGF1,FGF2,FGFR1,FGFR2,ERK1,ERK2 mRNA in the lung tissue,and reduce the degree of pulmonary fibrosis of rats with idiopathic pulmonary fibrosis,but the effect of single medicine is not as good as prednisone,the effect of combined application of prednisone and Fuwei ointment is better.