| Objective: Diffuse interstitial lung disease(DILD)is also called pulmonary fibrosis(PF).It is a kind of immune-mediated chronic inflammation diseases, which is characterized by the infiltration of mononuclear macrophage,leucocyte,lymphocyte, proliferation of fibroblast and deposition of fibrosis connective tissue in the alveola interstitia.In resent years, the incidence and mortality have been elevating in the world. Idiopathic pulmonary fibrosis(IPF) is the prototypical interstitial lung disease.At present, corticosteroid, immunosuppressive agent and anti- fibrosis agent were used for treatment of IPF,but the effects are not satisfying.Therefore, the focus of present study is to explore effective method.This study aimed to observe the effect of spironolactone on bleomycin-induced pulmonary interstitial fibrosis in rats, and discuss the mechanisms of aldosterone( ALD), which lead to PF, through detecting the levels of ALD and transforming growth factor-β1(TGF-β1) in lung tissue and plasma respectively. The correlation between them was analyzed so as to offer therapy support for aldosterone antagonist to treat pulmonary interstitial fibrosis.Methods: Forty-two male Sprague Dawley(SD) rats(provided by Center of Experiment Animal of Hebei Medical University)were randomly divided into three groups: normal control group(C group),bleomycin group(B group) and spironolactone group(T group). In B and T group, PF was induced in SD rats by intratracheal instillation of bleomycin,while C group was injected NS in trachea.The rats in B and C group received daily NS,and in T group spironolactone(100mg/kg)was perfused into stomach respectively on the same day.Six rats in each group were sacrificed on 7,14 and 28 days respectively after intratracheal instillation. The left lung was excised for HE,Masson Staining and detecting of lung coefficient. The level of TGF-β1 was measured by immunohistochemistry, and positive rate of TGF-β1 determined by sem quantitative picture analysis. The contents of collagen,ALD and TGF-β1 were detected in right lung tissue. The levels of ALD and TGF-β1 were detected in plasma and the correlation of them was analyzedResults lung coefficietThe lung coefficiet of B group on every time was higher than that of normal control (P<0.01).The lung coefficiet of T group increased compared with normal control on 7and14-day (P<0.05),while on 28d there is no significant difference compared with normal control. There were significant differences on every phrase in T group and B group compared with normal control(P<0.05或P<0.01). 2 HE/Masson Staining on the lung tissue The lung of normal control group rat had no change lesion in every point,but that of B group showed acute inflammation:there were a great deal of poly-cyte and monocyte infiltration in alveolar space and interstitia,company edema and slight hemorrhage.Alveoli normal structure was destructed by granulation in severe areas. Alveolitis relieved on the 14d, but hemorrhage and edema were still existing, with fibroblast increasing,interval widening obviously, collagen deposited and patches of fibrosis.In 28d-group, alveolitis did not decreased obviously. Alveola structure was destructed, with mass collagen deposited around neonate blood capillary. Alveolar interval and part of alveolar spacearea occupied by collagen and fibrin. Inflammatory cell in interstitia was mainly lymphocyte infiltration. Alveolitis of T and B group in every phase was markedly severe compared with normal control.While PF was significantly different from normal control just on 14 and 28d.T group has the same tendency as B group;but the degree of alveolitis and pulmonary fibrosis decreased.These results suggested spironolactone may relieve alveolitis and PF induced by bleomycin in rats.3 HYP concentrationHYP concentrations of B group and T group were both higher then normal control(P<0.01).But that of B group increased gradually ;That of T group took on low level,but increased too,HYP was lower than that of B group on 7d but there w... |
