布地奈德雾化吸入干预博莱霉素致大鼠肺纤维化实验研究

Interventional therapy of blemycin-induced pulmonary fibrosis by inhaled budesonide in rats

目的探讨布地奈德(budesonide,BUD)雾化吸入对博莱霉素所致大鼠肺纤维化模型的干预作用。方法 60只SD大鼠随机分为雾化吸入BUD 0.5mg/kg者为干预1组、雾化吸入BUD 1mg/kg者为干预2组、肺纤维化模型组(模型组)、生理盐水对照组(对照组)各15只。干预1组,干预2组和模型组采用气管内滴注博来霉素建立肺纤维化大鼠模型,对照组采用生理盐水滴注。0～6d每天雾化吸入,干预1组和干预2组雾化吸入BUD,模型组和对照组雾化吸入生理盐水。分别于7,14,28d后每组各处死大鼠5只,进行肺组织形态学观察、肺系数测量、病理HE和Masson染色评价其肺组织肺泡炎及肺纤维化程度。结果肺系数、肺泡炎和肺纤维化程度干预1组第7天与模型组比较差异无统计学意义(P>0.05),第14,28天低于模型组(P<0.05);干预2组各时间点大鼠肺系数、肺泡炎和肺纤维化程度均明显低于模型组及干预1组(P<0.05)。结论雾化吸入BUD可减轻中、后期博莱霉素致大鼠肺泡炎和肺纤维化程度,加大BUD雾化吸入剂量可减轻前期肺泡炎,缓解后期肺纤维化的产生。

Objective To explore the intervention effect of inhaled budesonide on blemycin-induced pulmonary fibrosis in rats. Methods A total of 60 SD rats were randomly divided into intervention group 1 receiving aerosol in halation of 0.5 mg/kg budesonide, intervention group 2 receiving aerosol inhalation of 1 mg/kg budesonide, model group and control group, with 15 rats in each group. The rat models of pulmonary fibrosis were induced by intratracheal instillation of bleomycin in intervention groups, and model group, and control group received by intratracheal instillation of normal saline. The rats in intervention groups inhaled budesonide, and model group and control group inhaled normal saline for 6 days. Five rats in every group were sacrificed by day 7, 14 and 28 to evaluate the degrees of alveolar inflammation and pulmonary fibrosis by observing the morphological change of lung tissue, measuring the lung coefficient, and HE and Masson staining. Results The lung coefficients, degrees of alveolar inflammation and pulmonary fibrosis in intervention group 1 were not significantly different from those in model group by day 7（P〉0. 05）, and lower than those in model group by day 14 and 28（P〈0.05）. And the above indexes were significantly lower in intervention group 2 than those in model group and intervention group 1 at every time point （P〈 0.05）. Conclusion Aerosol inhalation of budesonide can reduce the degree of alveolar inflammation and pulmonary fibrosis induced by bleomycin in the middle and late period. Increase of budesonide aerosol inhalation dose can reduce alveolar inflammation in the early period and relieve the pulmonary fibrosis in the late period.