孟鲁司特联合强的松对博莱霉素诱导的肺纤维化大鼠模型的干预作用

Intervention of Montelukast plus Prednisone on Bleomycin-induced acute exacerbation of pulmonary fibrosis in rats

摘要:

目的  研究孟鲁司特联合强的松对博莱霉素诱导的肺纤维化（PF）大鼠模型的干预作用。方法  将60只Wistar大鼠随机分成5组，即空白对照组、模型对照组、孟鲁司特（MK）组、强的松组及联合干预组。空白对照组以生理盐水0.2 ml注入气管内，其余4组以气管内滴注博莱霉素（5 mg/kg）建立PF模型。分别在造模后第7天和第28天5组各处死6只大鼠取材。采用苏木精-伊红和Masson染色法观察肺组织纤维化改变，酶联免疫吸附试验检测血清结缔生长因子（CTGF）、转化生长因子β1（TGF-β1）的水平，免疫组织化学法染色检测肺组织中CTGF和TGF-β1的表达水平。结果  联合干预组和模型对照组比较，第7天肺泡炎评分为（1.63±0.16）和（2.73±0.15），第28天肺间质纤维评分（1.66±0.10）和（2.76±0.13）分，差异有统计学意义（P <0.01）。第7天，各组肺组织TGF-β1表达水平均低于模型对照组，差异有统计学意义（P <0.05）。第28天，各组肺组织CTGF、TGF-β1表达水平均低于模型对照组，差异有统计学意义（P <0.01）。第7天、第28天血清中CTGF和TGF-β1水平均低于模型对照组，差异有统计学意义（P <0.01）。结论  MK联合强的松更能显著减轻大鼠肺组织肺泡炎及PF程度，其机制与降低血清及组织中CTGF和TGF-β1的表达水平相关。

Abstract:

Objective To study the intervention of Montelukast plus Prednisone in a rat model of pulmonary fibrosis (PF) induced by Bleomycin. Methods Sixty Wister rats were randomly divided into 5 groups including blank control, model control, Montelukast, Prednisone and combined Montelukast and Prednisone treatment groups. Pulmonary fibrosis model was induced by Bleomycin. The rats were sacrificed on the 7th and 28th day after modeling respectively. The degrees of lung inflammation and pulmonary fibrosis were detected by hematoxylin and eosin staining and Masson staining. The serum levels of connective tissue growth factor (CTGF) and TGF-β1 were assessed by enzyme-linked immunosorbent assay. The expressions of CTGF and TGF-β1 in lung tissues were evaluated by immunohistochemical staining. Results The scores of alveolitis in the model control group and the Montelukast group on day 7 were (1.63 ± 0.16) and (2.73 ± 0.15) respectively, the difference was significant between the two groups (P < 0.01). The scores of pulmonary fibrosis in the model control group and the Montelukast group on day 28 were (1.66 ± 0.10) and (2.76 ± 0.13) respectively, the difference was significant between the two groups (P < 0.01). On day 7, the TGF-β1 level in the lung tissues of the blank control, Montelukast, Prednisone and combined Montelukast and Prednisone treatment groups decreased as compared to the model control group with significant differences (P < 0.05). Compared with the model control group, the CTGF and TGF-β1 levels in the lung tissues of other groups significantly decreased on day 28 (P < 0.01). On day 7 and 28, the serum levels of CTGF and TGF-β1 in the model control group were significantly higher than those of other groups (P < 0.01). Conclusions The combined treatment of Montelukast and Prednisone can alleviate alveolitis and pulmonary fibrosis induced by Bleomycin, and its mechanism is associated with the reduced CTGF and TGF-β1 expressions in lung tissues.