摘要
目的探讨醛固酮拮抗剂减轻大鼠肺纤维化的作用机制。方法36只雄性SD大鼠气管内滴入博莱霉素A_5复制肺纤维化模型后,分为螺内酯干预组(螺内酯100mg·kg^(-1)·d^(-1))和模型组,另取6只雄性SD大鼠为正常对照组。各组动物于造模后第7、14、28天分别处死6只。通过HE染色、Masson染色观察肺组织形态的变化、测定肺组织及血浆醛固酮(ALD)含量及肺组织中羟脯氨酸(HYP)浓度来评价治疗效果。测定血浆及肺组织匀浆中转化生长因子β_1(transforming growth factor-β_1,TGF-β_1)含量。结果①模型组和干预组血浆、肺组织ALD水平较正常对照组均升高(P＜0．05,P＜0．01)；②干预组肺组织HYP含量较模型组明显下降(P＜0．01)；③HE染色、Masson染色可见干预组肺纤维化程度明显低于模型组；④各时间点模型组血浆TGF-β_1含量均较正常对照组及干预组明显增高(P＜0．01)；各时间点干预组血浆TGF-β_1含量高于正常对照组,但两组比较差异无显著性(P＞0．05)；肺组织匀浆与血浆各时间点TGF-β_1含量变化一致。⑤相关分析表明模型组各时间点血浆ALD水平与TGF-β_1含量呈正相关：7天(r =0．901,P＜0．05)；14天(r=0．942,P＜0．01)；28天(r=0．826,P＜0．05)。结论螺内酯可能是通过抑制TGF-β_1产生来减轻大鼠肺纤维化程度。
Objective To investigate the mechanisms of aldosterone antagonist on attenuating pulmonary fibrosis in the rats. Methods The rats were randomly divided into control（group C） ,pulmonary fibrosis（group B） and spironolactone prevention groups（group T）. Rats pulmonary fibrosis was induced by endotracheal injection of bleomycin As. Then the rats received spironolactone （100mg · kg^-1 · d^-1） in group T or normal Saline（group B and C） by instilling into the stomach, six rats in each group were sacrificed on 7, 14,28 days respectively after intratracheal instillation. Histological changes of the lungs were evaluated by HE staining and Masson＇s trichrome staining. Collagen content of the lung tissue was assessed by hydroxyproline（HYP） concentration. Transforming growth factor-β1 （TGF-β1）level of plasma was measured by ELISA. Results （1）Aldosterone levels of plasma and tissue in group T and group B were significantly higher than those in group C（ P 〈0.05, P 〈0.01） （2）HYP concentration of the lung in group T was lower than that in group B （P 〈 0.01）; （3）Compared with group B, the grade of pulmonary fibrosis was significantly decreased in group T（ P 〈0.01） ;（4）TGF-β1 concentration of plasma in group B at every time point was much higher than that in normal control and group T（ P 〈0.01）. TGF-β1 of plasma in group T was higher than that of control group at every time point, but was no significant difference（ P 〉0.05）. The change of TGF-β1 in the lung tissue was same as that of plasmas （5）The level of plasma aldosterone was positively related with the concentration of plasma TGF-β1 in pulmonary fibrosis group：seven day（ r = 0.90, P〈0.05）;fourteen day（r =0.94, P 〈0.01）s twenty-eight day（r =0.83, P 〈0.05）. Conclusions Spironolactone can attenuate pulmonary fibrosis in the rats, which may be through inhibiting the concentration of plasma TGF-β1.
出处
《国际呼吸杂志》
2006年第7期490-492,498,共4页
International Journal of Respiration
基金
河北省卫生厅科技攻关项目(2003035)
