厄多司坦对博莱霉素致大鼠肺纤维化发生发展的干预作用

The Effects and Mechanisms of Erdosteine in Bleomycin-Induced Pulmonary Fibrosis in Rats

目的：探讨厄多司坦对肺纤维化的干预作用及机制。方法：清洁级雄性SD大鼠24只,随机分为2组：博莱霉素组12只（气管内滴注博来霉素复制肺纤维化模型5mg/kg,0.2-0.3mL）、厄多司坦组12只（造模后用厄多司坦10mg/kg·d灌胃）,各组于造模后第7、28d行肺功能检查后各处死6只,观察肺泡炎和肺纤维化的动态变化和肺组织匀浆中羟脯氨酸（HYP）、丙二醛（MDA）、髓过氧化物酶（MPO）含量及超氧化物歧化酶（SOD）活力。结果：①厄多司坦组大鼠肺泡炎、肺纤维化程度减轻,肺功能优于博来霉素组。②28d时肺组织匀浆中HYP含量厄多司坦组（5.93±0.24）显著低于博来霉素组（6.36±0.27）（P〈0.05）。③7d时肺组织匀浆中MDA、MPO含量厄多司坦组显著低于博来霉素组（P〈0.01）,厄多司坦组SOD活力高于博来霉素组（P〈0.01）,28d时上述各指标两组间无统计学差异（P〉0.05）。结论：①厄多司坦对博莱霉素致大鼠肺纤维化有干预作用,②厄多司坦干预肺纤维化的机制早期可能为通过使中性粒细胞扣压减少,增加自由基的清除使体内氧化-抗氧化系统恢复平衡,使脂质过氧化损伤减轻而实现的。

Objective： To investigate the possible effect and understand mechanisms of erdosteine in pulmonary fibrosis. Method：24 Sprague-Dawley male rats weighting 250±10g were randomly divided into two groups：BLM group twelve rats（Lung fibrosis was induced by intratrached injection of BLMA5 5mg/kg,0.2- 0.3mL） ,erdosteine group twelve rats（injected erdosteine （10mg/kg） into oesophagus once a day from lung fibrosis to induce sacrifice,killed randomly at 7th day and 28^th day（n： 6,at each time point）by puncturing heart to obain blood. All rats were analyzed pulmonary function before they were killed and the extent of alveolitis and collagen deposition were obsarved,The left lung tissue homogenate was used to determine the content of HYP, MDA, MPO and the activity of SOD of lung tissue. Results： ①The degree of alveolitis and fibrosis of erdosteine group was alleviated compared to that of corresponding BLM group significantly（P〈0.05）, and pulmonary function of erdosteine group rats was surpassive significantly in BLM group. ②At the 28th day in erdosteine group the content of HYP in lung tissue（μg/mg）was lower significantly than that of corresponding BLM group（P〈0. 05）. OAt the 7th day in erdosteine group the content of MDA,MPO in lung tissue（μg/mg） was lower significantly than that of corresponding BLM group,and the activity of SOD in lung tissue （U/mg prot） was higher significantly than that of BLM group（P〈0.01） ,but At 28th day there was no statistic difference（P〉0. 05）Conclusion： ①Erdosteine can cure Bleomycin-induced pulmonary fibrosis in rats. ②The possible underlining mechanisms that Erdosteine cure Bleomycin-induced pulmonary fibrosis in rats may decrease neutrophile accumulation, balace oxidation-antioxidation system by reducing free radical production and increasing free radical remove,to alleviate lipid peroxidation damage.