沐舒坦对大鼠肺纤维化模型的干预及可能机制

Ambroxol in the Rat Model of Bleomycin-induced Pulmonary Fibrosis and Its Possible Mechanism

目的观察沐舒坦对博来霉素A5所致大鼠肺纤维化的干预作用及其可能机制,为肺纤维化的治疗探索一种新方法。方法雌性Wistar大鼠60只,随机分成3组,每组20只。B组为博来霉素模型组,气管内一次性注入博来霉素5mg/kg体重,复制肺纤维化模型;A组为沐舒坦干预组,于博来霉素灌注后次日,予沐舒坦35mg/kg腹腔内注射;N组为正常对照组,予等量生理盐水做对照。3组动物均在气管内灌药后第3、7、14、28天各随机处死5只,提取肺组织。通过苏木素-伊红染色观察肺组织肺泡炎程度及Masson染色观察基质胶原变化来评价治疗效果。用放免法测定肺组织匀浆中TNF-α含量,以求在分子水平上探讨沐舒坦干预鼠肺纤维化的可能机制。结果①B组大鼠肺泡炎及肺纤维化程度明显高于N组,差异有显著性(P<0.05),同时将A组与B组做比较,其肺泡炎及肺纤维化程度于灌药后第14、28天显著低于B组,而第7天虽亦低于B组,但差异无显著性(P>0.05);②肺组织匀浆中TNF-α含量测定显示B组明显高于N组,而A组TNF-α含量于灌药后第7、14、28天明显低于B组,但仍高于N组。结论沐舒坦对博来霉素所致大鼠肺纤维化具有明显治疗作用,且这种作用有可能是通过抑制TNF-α来实现的。

Objective To investigate the therapeutic effect of ambroxol in bleomycin - induced pulmonary fibrosis of rats, Methods Sixty Wistar rats were divided into three groups：The normal control group（ group N ） , the model group treated with bleomycinA5 （group B） and the group treated with ambroxol（ group A）. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin. Then the rats received daily ambroxol 35mg/kg（ group A） ,or normal saline（ group B）. Five rats in each group were killed on 3.7.14 and 28 days after intratracheal instillation. Histological changes of the lungs were evaluated by liE stain and Masson＇s trichrome stain. The levels of tumor necrosis factor - α （ TNF - α） in lung homogenates were measured by radioimmunoassay. Results Pulmonary fibrosis of Group A was significantly improved as compared with that of Group B （ P 〈 0.05 ）. It was also found the content of tumor necrosis factor - a in Group A is lower than in Group B （ P 〈 0.05 ）, Conclusions Ambroxol alleviates bleomycin - induced pulmonary fibrosis in rats. Inhibiting the release of TNF - aln lung tissues may be one of the mechanisms.