阿奇霉素对肺间质纤维化大鼠干预作用的研究

目的 探讨阿奇霉素对博莱霉素所致大鼠肺间质纤维化的干预作用及机制。方法 雄性Ｗｉｓｔａｒ大鼠４２只,分为３组。博莱霉素模型组：１８只,大鼠气管内一次性注入博莱霉素５ｍｇ／ｋｇ,制成肺间质纤维化模型,阿奇霉素治疗组：１８只,模型制备同博莱霉素模型组,模型制备２小时后,顷胃管注入阿奇霉素８０ｍｇ／ｋｇ,每日１次,每周连续３日。两组动物于１、２和４周处死。对照组：６只,大鼠气管内注入生理盐水０．５ｍｌ,

An experimental study on the effect of azithromycin treatment in bleomycin-induced pulmonary fibrosis of rats

OBJECTIVE: To evaluate the therapeutic effects and mechanism of azithromycin treatment in bleomycin-induced pulmonary fibrosis of rats. METHODS: Animal model of bleomycin-A5-induced pulmonary fibrosis was established in rats.36 animal models were divided into two groups: a bleomycin-induced pulmonary fibrosis group and a azithromycin group in which the animal models were treated with azithromycin (80 mg/kg once a day for three continuous days in a week). The animals of the two groups were killed at the first,second and fourth week respectively.Another six rats constituted a normal control group, instillated withsaline intratracheally and killed at the first week. Pathological changes activity of nuclear factor kappaB (NF-kappaB) of alveolar macrophage, cytokine tumor necrosis factor (TNF) alpha, transforming growth factor-beta (TGF-beta) mRNA expression and protein levels of alveolar macrophage and lung tissue were studied or measured. RESULTS: Amelioration of alveolitis and lung fibrosis after treatment with azithromycin was shown in pathological section (P < 0.05). The activity of NF-kappaB was significantly higher in one-week pulmonary fibrosis model than that in normal control and its level in alveolar macrophage reduced (67.2%) after treatment with azithromycin. The level of protein and mRNA of TNFalpha, TGF-beta in lung tissue and alveolar macrophage was increased in the early stage of pulmonary fibrosis and reduced after treatment with azithromycin (P < 0.05). CONCLUSION: It is suggested that azithromycin might be a therapeutic drug for pulmonary fibrosis in the future. Azithromycin reduced the degree of alveolitis and fibrosis through inhibition of the activity of NF-kappaB and the expression of TNFalpha, TGF-beta mRNA and lowering the level of protein in alveolar macrophage and lung tissue in the early stage of pulmonary fibrosis. This might be one of the mechanisms of azithromycin treatment in pulmonary fibrosis.