吸入环孢素A对大鼠肺纤维化的干预作用

Effect of Inhalation of Cyclosporin A on Bleomycin-Induced Pulmonary Fibrosis in Rats

目的 :研究吸入环孢素A(CsA)对大鼠肺纤维化的干预作用及可能的作用机制。方法 :Wistar大鼠经气管内注入博莱霉素诱导肺纤维化 (M组 ) ,实验组 (A组 )次日雾化吸入CsA进行干预 ,对照组 (C级 )用生理盐水。各组注药后 7d和 2 8d分别处死 5只。测肺系数 ,观察肺泡炎及肺纤维化的程度。检测血及肺泡灌洗液 (BALF)中单核细胞趋化因子 1(MCP 1)和转化生长因子 β(TGF β)。 结果 :M组、A组与C组比较肺系数明显增加 (P <0 .0 5 )。C组肺泡结构正常 ,M组 7d时以肺泡炎改变为主 ,2 8d时广泛性肺纤维化为主。A组病理改变与M组相似 ,但程度较轻。 7d时血清TGF βM组明显高于C组及A组 (P <0 .0 1)。 2 8d时血清及BALF中TGF βM组明显高于C组及A组 (P <0 .0 1) ;MCP 1血清中M组明显高于C组及A组 (P <0 .0 5 ,) ;BALF中M组及A组明显高于C组 (P <0 .0 1)。结论 :雾化吸入CsA能减轻大鼠肺纤维化 ,可能通过抑制TGF β和MCP

Objective: Our aim was to study the effect of inhalation of cyclosporin A (CsA) on bleomycin-induced pulmonary fibrosis in rats and its possible mechanism. Methods :Pulmonary fibrosis was induced in Wistar rats by intratracheal instillation of bleomycin (group M).In the test group (group A) the rats inhaled CsA daily from the next day of received bleomycin. Normal controls (group C) received normal saline both intratracheally and from inhalation. Five rats in each group were killed 7 and 28 days after intratrachael instillation. Histological changes in lung were evaluated by the methods which Szapiel had used. The concentrations of monocyte chemoattractant protein-1 (MCP-1) and translation growth facter-β (TGF-β) in serum and BALF were determined. Results:The lung coefficients of group M and group A were increased. The alveolus structure of group C was normal. The pulmonary fibrosis degree of group A was less than that of group M. On the 7th day, the TGF-β concentration in serum of group M was higher than that of group A and C (P< 0.01). On the 28th day, the TGF-β in serum and BALF of group M were more than those of group A and C (P<0.01). MCP-1 in serum of group M was also higher than that of group A and C, and in BALF of group M and A, it was higher than that of group C. Conclusion:Inhalation of CsA alleviates bleomycin-induced pulmonary fibrosis in rats. The mechanism may be related to the changes of TGF-β and MCP-1.