| Idiopathic pulmonary fibrosis (IPF), a reason-unknown disease, is an immunity-mediated inflammation, of which the pathologic characters are diffuse alveolitis, disorder of alveolar structures and pulmonary interstitial fibrosis in the end. It has a bad prognosis and a high mortality. The average survival rate after the last diagnosis is about four years. There are no effective treatments at present. Therefore, it becomes the most important disquisitive aspect that finding the methods of curing IPF, especially medication.Objective: Observe whether oxidation indexes changes exist in homogenate from bleomycin-induced pulmonary fibrosis rats; Study the effects and mechanisms of losartan in curing Bleomycin-induced pulmonary fibrosis of rats; furthermore compared with glucocorticoid, approach therapeutic efficacy of losartan in curing Bleomycin-induced pulmonary fibrosis.Method : 60 Sprague-Dawley male rats weighting 250±10g were randomly divided into four groups. (1)Control group (A group): 6 rats, were injected saline in trachea and oesophagus, and killed at 7th day. (2)BLM group (B group): 18 rats. Lung fibrosis was induced by intratrached injection of BLMA5 (5mg/kg, 0.2-0.3ml). They were given saline injection into oesophagus once a day, killed randomly at 7th day, 14th day and 28th day (n=6, at each time point). (3)Losartan group (C group): 18 rats were injected losartan(10mg/kg)into oesophagus once a day after BLM given, and killed ditto.(4) dexamethasone group(D group): 18 rats were injected dexamethasone(3mg/kg) into abdominal cavity once a day after BLM given, and killed ditto. Before killed, the rats were executed pulmonary function test for record forced vital capacity (FVC) and pulmonary compliance, and then killed by puncturing heart to obtain blood; the right lung was preserved in 10% formalin for histologic interpretation. HE pigmentation was performed to observe alveolitis, Masson pigmentation was used to look into the extent of collagen deposition. Alveolitis and lung fibrosis were classified by the method of Szapiel. Left lung was resected by made homogenate.Result: 1. The activity of SOD in lung tissue (U/mgprot): The activity of SOD of B7,B14 group was lower than that of A group significantly(P<0.05), The activity of SOD of A28 group is the highest in the four groups. The activity of B28 group is the lowest in the four groups. There were no significant differences among C28, D28, B28 and A group. The activity of SOD of D7,D14 group was higher than that of B group significantly(P<0.01), The activity of SOD of C group is higher than D group, The activity of SOD of C7 group is higher than D 7 group significantly(P<0.05). 2. The content of MDA in lung tissue (nmol/mgprot): The content of MDA of B7,B14 group was higher than that of A group significantly(P<0.01), The content of MDA of A28 group is the lowest in the four groups. The content of B28 group is the highest in the four groups. There were no significant differences among C28, D28, B28 and A group. The content of MDA of D7,D14 group was lower than that of B group significantly(P<0.01), The content of MDA of C group is lower than D group, The content of MDA of C7 group is lower than D7 group significantly(P<0.05). 3. The content of MPO in lung tissue (U/gprot): The content of MPO of B7 reached the peak level, after that the level decreased gradually, The content of MPO of B7,B14 group was higher than that of A group significantly(P<0.01), The content of MPO of A28 group is the lowest in the four groups. The content of B28 group is the highest in the four groups. There were no significant differences among C28, D28, B28 and A group. The content of MPO of D7,D14 group was lower than that of B group significantly(P<0.01), The content of MPO of C group is lower than D group, but there was no statistic differences. 4. The content of NOS in lung tissue(U/mgprot): The content of NOS of B7 reached the peak level, after that the level decreased gradually, The content of NOS of B7,B14 group was higher than that of A group significantly(P<0.01), The content of NOS of A28 group is the lowest in the four groups. The content of B28 group is the highest in the four groups. There were no significant differences among C28, D28, B28 and A group. The content of NOS of D7,D14 group was lower than that of B group significantly(P<0.01), The content of NOS of C group is lower than D group, The content of NOS of C7 group is lower than D7 group significantly(P<0.05).5 5.1 The numerical value of FVC of B group was lower than that of A group significantly(P<0.01), the numerical value of FVC of D group was higher than that of B group(P<0.05),the numerical value of FVC of C group was higher than that of D group(P<0.05).5.2 The numerical value of pulmonary compliance of B group was lower than that of A group, the numerical value of pulmonary compliance of D group was higher than that of B group(P<0.05),the numerical value of pulmonary compliance of C group was higher than that of D group(P<0.05). 6. The change of pathomorphology of lung: The lung tissues of each B group and C group display the pathological process of alveolitis and fibrosis, these pathological changes proved the PF rat models induced by blemycin was successfully duplicated. The degree of alveolitis and fibrosis of D group were alleviated compared to that of corresponding B group, compared with D7 and B7, the degree of alveolitis was alleviated significantly (P<0.01), compared with D14and B14, the degree of alveolitis was alleviated significantly (P<0.05), compared with D28and B28, the degree of fibrosis was alleviated significantly (P<0.05).In the serious degrees of alveolitis and fibrosis, the numbers of C groups were less than that of D groups, but there was no statistic differences. Conclusion : 1.In the course of BLM-induced rat pulmonary fibrosis, the activity of SOD in lung tissue decrease, the content of MDA,the content of MPO,the content of NOS in lung tissue increase, the numerical value of pulmonary compliance and FVC in lung tissue decrease. 2. Losartan can alleviate alveolitis and lung fibrosis, can increase the activity of SOD in lung tissue, can decrease the content of MDA,the content of MPO,the content of NOS in lung tissue increase, can increase the numerical value of pulmonary compliance and FVC in lung tissue decrease. 3. Losartan can alleviate BLM-induced rat pulmonary fibrosis by antioxidant effect and improve the pulmonary ventilation function. |
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