红霉素对肺纤维化大鼠核因子κB活性及细胞因子mRNA表达的影响

The effect of erythromycin on NF κB activation and cytokines mRNA expression in bleomycin induced pulmonary fibrosis in rats

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：正常对照组、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服红霉素（１００ ｍｇ／ｋｇ）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（ＡＭ） 的核因子（ＮＦ）κＢ活性；用Ｎｏｒｔｈｅｒｎ 杂交测定肺组织的白细胞介素１（ＩＬ１）β和转化生长因子（ＴＧＦ）βｍＲＮＡ表达。结果红霉素治疗组第４ 和第７ 天时，ＡＭ 的ＮＦκＢ活性与博莱霉素模型组比较，差异有显著性（Ｐ＜０－０５） ，第７ 天时肺组织的ＩＬ１β和ＴＧＦβｍＲＮＡ表达与博莱霉素模型组比较，差异有显著性（ Ｐ＜０－０５）。在病理上，红霉素减轻了肺泡炎及后续的肺纤维化。结论 在肺纤维化中，红霉素可能通过抑制ＮＦκＢ活性、ＩＬ１β和ＴＧＦβｍＲＮＡ表达起抗炎和抗纤维化作用。

Objective To evaluate the effect of erythromycin (EM) on nuclear factor κB (NF κB) 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 4 th, 7 th and the 28 th day separately NF κB activation in alveolar macrophages (AM) was investigated by electrophoretic mobility shift assay The expressions of IL 1β and TGF β 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 4 th and 7 th day, the activities of NF κB 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 7 th day, the expressions of IL 1β and TGF β 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 κB is involved in the inflammatory response in BLM induced pulmonary fibrosis in rats, EM has inhibitory effect on NF κB activation, IL 1β and TGF β mRNA expression, by which it ameliorated acute lung injury and fibrosis those tested rats