吸入环孢菌素A对肺纤维化及其气道高反应性的干预作用

Effects of cyclosporin A aerosol on pulmonary fibrosis and airway hyperresponsiveness in rats

目的检测博莱霉素致肺纤维化大鼠气道高反应性的形成,观察吸入环孢菌素A对肺纤维化及其气道高反应性的治疗作用。方法雄性Wistar大鼠36只,按随机数字表法分为对照组(A)、模型组(B)、药物组(C)3组,每组12只。检测博莱霉素致肺纤维化大鼠模型吸入环孢菌素A治疗前后转化生长因子β(TGF-β)和肺匀浆羟脯氨酸(HYP)的含量,并使用大鼠呼吸机及气道压力监测仪测量各组大鼠气道压力峰值-时间指数(APTI)的差异。结果A组肺泡结构正常,B组28 d时广泛的肺纤维化为主。C组病理改变与B组相似,但程度较轻。28 d B组血清中TGF-β及肺匀浆中HYP的含量显著高于A组(P<0.01),而且与C组血清中的含量相比有差别(P<0.05);B组APTI与A组、C组比较(mACh为0.05 mg/kg时,三者分别为0.508,0.841,0.671 mmHg/s),差异有显著性(P<0.05)。结论博莱霉素致肺纤维化大鼠模型存在气道高反应性,吸入环孢菌素A可减轻肺纤维化程度,降低气道高反应性。

Objective To explore cyclosporin A aerosol for anti-airway hyperresponsiveness in bleomycin-induced pulmonary fibrosis. Methods Thirty-six male healthy Wistar mice were randomly divided into 3 groups： group A （control, n = 12）, group B （treated with bleomycin, n = 12）, and group C （treated with cyclosporin A aerosol, n = 12）. Hydroxyproline（HYP） in lung tissue, serum concentration of transforming growth factor-β（TGF-β） and airway pressure time index（APTI） were measured. Results Alveolar structure of group A was normal. Pttlmonary fibrosis degree was less in group C than in group B. At day 28, HYP in lung tissue and serum TGF-β were more in group B than in groups A and C（ P 〈 0.01）. Compared with group A（0. 508 rnrnHg/s） and group C （0. 671 mmHg/s）, APTI was significanfly higher in group B（0. 841 mmHg/s）. Conclusion Airway h： exists in rats with bleomycin-induced pulmonary fibrosis. Inhalation of CsA alleviates Neomycin-induced pulmonary fibrosis and reduces airway hyperresponsiveness in rats.