雾化吸入地塞米松对肺纤维化大鼠肺巨噬细胞凋亡的影响

Influence of inhaled dexamethasone on pulmonary macrophage apoptosis of the bleomycin-induced lung fibrosis in rats

目的通过观察雾化吸入地塞米松对肺间质纤维化大鼠的肺巨噬细胞凋亡的影响,了解局部吸入激素是否能达到(或超过)全身应用激素的疗效。方法用一次性气管内注入博莱霉素法制作动物肺纤维化模型,对肌注地塞米松(DXM)组和雾化吸入DXM组肺组织病理标本凋亡细胞定性(HE染色光镜观察肺泡炎和肺纤维化程度)和定量(DNA片段原位缺口末端标记法进行凋亡细胞定量)进行比较分析。结果肌注DXM组肺巨噬细胞的凋亡明显高于博莱霉素对照组,说明DXM通过诱导肺内炎性细胞的凋亡而达到减轻肺泡炎,防止纤维化形成的作用。雾化吸入DXM同样可以诱导肺巨噬细胞的凋亡,与肌注DXM组相比无显著性差异,且雾化吸入DXM组大鼠一般情况较好,说明局部应用激素耐受性好,且吸入激素治疗具有作用直接、迅速,且全身副作用少的优点。结论吸入激素与全身应用激素同样可促进肺巨噬细胞的凋亡,减轻博莱霉素所致的肺纤维化。因此,临床上吸入激素可试用于ILD的治疗。

Objective To explore the effect and mechanism of inhaled and systemic administering dexamethasone on pulmonary macrophage apotosis of the bleomycin-induced lung fibrosis in rats. Methods 60 Sprague-Dawley rats were divided randomly into three groups including bleomycin-induced lung fibrosis group（Group A, n = 20）, inhaled dexamethasone group （Group B, n = 20） and intramuscular injection of dexamethasone group （Group B, n= 20）. Each group was again divided into four subgroups, which were sacrificed on 1,7,14or 28 day. Bronchoalveolar lavage fluid（BALF） was got and the cells counting as well as differentiation were figured out, HE stain was performed on the lung tissue sections to observe the extent of alveolitis and fibrosis, the semi-quantity of apoptosis cells in lung tissue was assay by in situ TUNEL （terminal deoxynucleotidy transferase-mediated dUTP nick endlabeling）. Results （1）Compared with group A, percentage of neutrophils in group B and C was lower （ P 〈0.05）. （2）Compared with group B and C,more severe fihrotic lesion was shown in the histological examination of the lung tissue sections of group A. （3）The apoptosis index （AI） of inflammatory cells in each subgroups of group B and C was higher than that in group A,and there were no significance between group B and C. Conclusions Inhaled dexamethasone can induce apoptosis of pulmonary inflammatory cells and ameliorate the formation of bleomycin-induced pulmonary fibrosis as well as systemic dexamethasone.