红霉素对肺纤维化大鼠核因子κB活性及细胞因子mRNA表达 …

目的 探讨红霉素治疗肺纤维化的机制和疗效。方法 实验用Ｗｉｓｔａｒ大鼠８１只，分成三组；正常一附属博莱霉素模型组和红霉素治疗组。每组２７只。气管内注入单剂量博莱霉素制备大鼠肺纤维化模型，于博莱霉素气管内注入后每日给予口红霉素治疗，各组动物分别于气管内用药后第４，７和２８天处死动物。用凝胶电泳迁移实验测定肺泡巨噬细胞的核因子（ＮＦ）－κＢ活性；

The effect of erythromycin on NF-kappa B activation and cytokines mRNA expression in bleomycin-induced pulmonary fibrosis in rats]

OBJECTIVE: To evaluate the effect of erythromycin (EM) on nuclear factor-kappa B (NF-kappa B) activation and cytokines mRNA expression in bleomycin-induced pulmonary fibrosis in rats. METHODS: Wistar rats were divided into three groups of 27 as follow: BLM-group received intratracheal instillation of single dose BLM 5 mg/kg. EM treated-group received intratracheal instillation of BLM 5 mg/kg and an oral instillation EM 100 mg.kg-1.d-1. Control group received intratracheal and oral instillation of normal saline. Animals of all three groups were sacrificed on the 4th, 7th and the 28th day separately. NF-kappa B activation in alveolar macrophages (AM) was investigated by electrophoretic mobility shift assay. The expressions of IL-1 beta and TGF-beta mRNA in lung were evaluated by Northern blot analysis. The pathological changes of lung tissue were analyzed quantitatively by computer gray scan. RESULTS: On the 4th and 7th day, the activities of NF-kappa B in AM were significantly increased in BLM-group compared with those of control group (P < 0.05), while they were significantly decreased in EM treated-group compared with BLM-group (P < 0.05). On the 7th day, the expressions of IL-1 beta and TGF-beta mRNA in lung were significantly decreased in EM treated-group compared with those in BLM-group. Pathologically, EM decreased exudation of inflammatory cells in the early response as well as degree of fibrosis in the late stage in the BLM-induced pulmonary fibrosis. CONCLUSIONS: These results indicate that NF-kappa B is involved in the inflammatory response in BLM-induced pulmonary fibrosis in rats, EM has inhibitory effect on NF-kappa B activation, IL-1 beta and TGF-beta mRNA expression, by which it ameliorated acute lung injury and fibrosis those tested rats.