Effects on Pulmonary Fibrosis in Rats After the Blockage of the Rennin-angiotensin-aldosterone System at Different Sites and Impact on the Expression of Monocyte Chemoattractant Protein-1

Objective To study the effects on pulmonary fibrosis in rats after the blockage of the rennin-angiotensin-aldosterone system at different sites and its mechanism. Methods Pulmonary fibrosis was induced in Sprague-Dawley(SD) rats by intratracheal instillation of bleomycin.Then the rats were perfused into stomach daily normal saline(group B),captopril 60 mg/kg(group C),losartan 10 mg/kg(group L),spironolactone(group S).Normal controls received normal saline both by intratracheal instillation and perfusion into stomach.Five rats in each group were sacrificed on 7,14,28 days respectively after intratracheal instillation.Histological changes of the lungs were evaluated by HE stain,Masson′s trichrome stain and hydroxyproline concentration of the lung tissue.The expression of monocyte chemoattractant protein-1(MCP-1)was measured by immunhistochemical method with image analyse system.Results (1) The level of lung fibrosis and alveolitis,positive rate of MCP-1 of lung tissues in rats of group C,S,L were significant lower than that in rats of group B,and the effects of the three drugs had no significant differences.(3)The effects of the three drugs had significant differences in hydroxyproline concentration of the lung tissue.Conclusion Captopril,spironolactone,losartan can all allevieate bleomycin-induced pulmonary fibrosis in rats.Inhibiting the expressions of MCP-1 in lung tissues may be one of the mechanisms.The effect of spironolactone to reduce collagen content in lung tissues was the best,and the effect of losartan was the worst in the three drugs.