Effect on paraquat-induced pulmonary fibrosis in rats after blockage of the rennin-angiotensin-aldosterone system at different sites

Objective To observe effects on paraquat-induced pulmonary fibrosis in rats after blockage of the rennin-angiotensin-aldosterone system at different sites by different drugs and to explore possible mechanisms.Methods Pulmonary fibrosis model was established by paraquat poisoning in SD rats by one-hit intragastrically with PQ 80 mg/kg.Then the rats were perfused into stomach and treated with daily normsaline(PQ group),captopril(60 mg/kg),losartan(10 mg/kg),spironolactone(100 mg/kg).Cotrol group received normal saline by perfusion into stomach.The rats in each group were sacrificed and lungs were harvested on each 7,14 or 28 d respectively.The degrees of pulmonary alveolitis and fibrosis were evaluated by HE staining and Masson Staining.Hydroxyproline(Hyp) concentration were detected and levels of protein expression of connective tissue growth factor(CTGF) of lung tissues were determined by immunohistochemistry staining with semquantitative picture analyse system.Results The scores of pulmonary alveolitis and fibrosis,hydroxyproline concentrations and the protein positive expression of CTGF of lung tissues in rats of each interfere group were significant lower than those in PQ group(P0.01).The effects of three drugs on hydroxyproline concentrations had significant differences(P0.05).Conclusion Captopril,losartan and spironolactone can all alleviate levels of pulmonary fibrosis caused by paraquat poisoning in rats,which may be due to inhibition of different receptors and protein expressions of CTGF.The effect of spironolactone to reduce collagen content in lung tissues was the best and effect of losartan was the worst.