盐酸氨溴索对新生大鼠高氧慢性肺损伤肺纤维化的干预研究

Effect of ambroxol on Pulmonary Fibrosis Caused by Hyperoxia in Neonatal Rats

目的探讨盐酸氨溴索对高氧性肺损伤新生大鼠肺组织纤维化的干预作用。方法出生12 h内的清洁级SD大鼠30只作为研究对象,随机分成3组(每组10只):空气对照组(A组)、高氧组(B组)、高氧加盐酸氨溴索组(C组)。除A组外,B组和C组均建立高氧肺损伤动物模型。C组新生大鼠每天腹腔注射溶于9 g/L氯化钠溶液中的盐酸氨溴索[20 mg/(kg.d)],A、B组新生鼠每日腹腔注射等量9 g/L氯化钠溶液,持续14 d。第14 d处死,取其肺组织切片,伊红染色法(HE)观察其肺组织病理变化;Masson三色染色图像定量分析计算其胶原纤维阳性面积百分比,酶联免疫分析法(ELISA法)测定肺组织Ⅲ和Ⅳ型胶原蛋白,判断其肺纤维化程度。结果 B组第14天肺组织病理发现间质细胞增多,肺泡数目减少,肺组织出现纤维化改变;C组肺组织病理改变明显减轻。与A组比较,B组Ⅲ型胶原及Ⅳ型胶原表达明显增多,胶原纤维阳性面积百分比明显增高(P<0.05)。C组与B组比较,Ⅲ型胶原及Ⅳ型胶原表达及胶原纤维阳性面积百分比明显下降(P<0.05)。结论盐酸氨溴索早期干预可减轻高氧性肺损伤新生大鼠的肺组织纤维化程度。

Objective To study the protective effect of ambroxol on pulmonary fibrosis caused by hyperoxia in neonatal rats.Methods Thirty Sprague-Dawley（SD） clean neonatal rats,which were less than 12 hours old,were enrolled in this study.The neonatal rats were randomly divided into3 groups： air-exposed control group（group A）;hyperoxia-exposed control group（group B）;hyperoxia-exposed plus ambroxol-treated group（group C）.The neonatal rats of group C were intraperitoneally injected with ambroxol [20 mg/（kg· d）] in solution of normal saline（NS）,group A and group B were intraperitoneally given the same dose of NS.On14th day,10 rats of each group were killed,the pulmonary pathological changes were observed by HE staining under light microscope.The area percentages of collagen fibers were measured by Masson staining and imaging analysis,and the protein content of collagenⅢand Ⅳwere detected by ELISA,respectively.Results On the 14th day of the exposure,the histopathologic examination demonstrated broadened lung interstitium and reduced alveolar quantity and lung fibrosis were developed in group B;ambroxol treatment obviously alleviated the changes of lung histomorphology.At the 14th day of the exposure to hyperoxia,the neonatal rats of group B had a significant increase in the area percentage of collagen fibers and protein content of collagen Ⅲ and Ⅳ compared with those in group A（P0.05）;the area percentage of collagen fibers and the protein content of collagen Ⅲ and Ⅳ in group C had a significant reduction compared with those in group B（P0.05）.Conclusion Early use of ambroxol can decrease the severity of the pulmonary fibrosis of neonatal rats exposed to hyperoxia