| Objective: Pulmonary fibrosis (PF) is a kind of serious lung diseases characterized by diffuse progressive fibroplasias and alveolar structure which finally leading to disorder of lung function ,and is the common final of many lung diseases .It has a bad prognosis and a high mortality , there is no satisfactory therapy for it up to now. Glucocorticoid and cytoyoxic drug are the fist choices in treating PF in clinic , but the therapeutic effect is indefinite accompanied with obvious side effect.So the urgent question which the scholar need to solve is to seek effective and safe medicine for treating PF. In this study , we interfere in the fibrosis process of PF rat model induced by bleomycin with aminoguanidine and the uintd of aminoguanidine and erdosteine, and observe the effects of aminoguanidine and erdosteine on lung function: breathing capacity and lung compliance and the changes in pathomorphology and content of HYP at different time point.we contrast to the result with orthodx Glucocorticoid therapy,the purpose is to study the treat result and joint action of aminoguanidine and erdosteine on experimental pulmonary fibrosis. As well as observe the effect of aminoguanidine and erdosteine on the content of MDA,MPO and the activity of SOD of lung tissue at different time point. The purpose is to explore the possible underlining mechanisms.Method:78 Sprague-Dawley male rats weighting 250±10g were randomly divided into four groups. (1)control group(A) group:six rats,were injected saline in trachea and oesophagus,and killed at 14th day. (2) BLM group(B)group: eighteen 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 and 14th day and 28th day(n=6,at each time point)by puncturing heart to obain blood.(3)Dexamethasone group (C) group:eighteen rats,were injected Dexamethasone(1mg/kg)into abdominal once a day after lung fibrosis was induced ,killed ditto.(4) aminoguanidine group(D)group: eighteen rats,were injected aminoguanidine(50mg/kg)into abdominal once a day from two days ahead of lung fibrosis was induced to sacrifice ,killed ditto.(5) uintd group of aminoguanidine and erdosteine(E)group: eighteen rats,were injected aminoguanidine ( 50mg/kg ) into abdominal and injected erdosteine (10mg/kg) into oesophagus once a day from two days ahead of lung fibrosis was induced to sacrifice ,killed ditto.The all rats were analysis pulmonary function at each time point before they were killed. After fixed in 4% paraform the right lung tissues were embedded in paraffin and sliced. Some of the sections were stained with HE and Masson staining to observe the extent of alveolitis and collagen deposition,the degrees of alveolitis fibrosis was classified by the method of Szapiel The left lung tissue homogenate were used to determine the content of HYP,MDA,MPO and the activity of SOD of lung tissue.Results:1Changes of pulmonary function1.1 breathing capacity ( cmH2o):A group breathing capacity was(12.23±0.2).B group breathing capacity at 7th day ,14th day and 28th day were(6.33±0.13),(6.13±0.16),(5.96±0.33),lower significantly than A group(P<0.01).C7 group(7.06±0.12)were lower significantly than A group (P<0.01)and were higher significantly than B7(P<0.05); C14 group(8.04±0.19)and C28 group(8.58±0.26)were higher than B14 groupand B28 group significantly(P<0.05)and were lower than A group significantly ( P<0.05 ) . D7 group(8.72±0.21)were lower significantly than A group (P<0.05)and were higher significantly than B7 group and C7 group(P<0.05);D14 group(9.47±0.11)were lower significantly than A group (P<0.05)and were higher significantly than B14 group and C14 group(P<0.05);D28 group(9.67±0.17)were lower significantly than A group (P<0.05)and were higher significantly than B14 group and C14 group(P<0.05).E7 group(8.83±0.25)were lower significantly than A group (P<0.05)and were higher significantly than B7 group and C7 group(P<0.05)but was not higher significantly than D7group(P>0.05),E14 group(10.93±0.08)and E28 group (11.2±0.1)were higher significantly than B14 group,C14 group,D14 groupand B group,C28 group,D28 group(P<0.05)and were lower significantly than A group(P<0.05).1.2 pulmonary compliance (ml/cmH2o) : pulmonary compliance of all group at 7th day were not significantly different, after that pulmonary compliance descend a little ,At 28th day pulmonary compliance were lowest. A group were( 0.221±0.016 ) .B7 group ( 0.188±0.021 ) were lower significantly than A group(P<0.05),B14 group(0.108±0.022)and B28 group(0.098±0.024)were lower significantly than A group(P<0.01).C7group(0.207±0.015)was not significantly change than A group and B7group(P>0.05),C14 group(0.132±0.038)and C28 group(0.128±0.011)were higher significantly than B14group and B28 group(P<0.05)and were lower significantly than A group ( P<0.01 ) .D7 group(0.210±0.018)was not significantly change than A group,B7group,C7group(P>0.05),D14group(0.186±0.027)and D28group ( 0.165±0.013 ) were higher significantly than B14group,C14group and D28group,C28group(P<0.05) and were lower significantly than A group(P<0.05).E7 group(0.218±0.028)were lower than A group and were higher than B7group,C7group,D7group ,but there were no statistic differe(P>0.05 ), E14 group ( 0.189±0.018 )were lower significantly than A group ( P<0.05 ) and were higher significantly than B14group,C14group(P<0.05),It was not significantly higher than D14 group(P>0.05),E28group ( 0.186±0.009 ) were lower significantly than A group (P<0.05)and were higher significantly than B28group,C28group,D28group(P<0.05).2 The content of HYP in lung tissue(ug/mg prot):A group(2.18±0.21).B7group(2.32±0.38)was not significantly higher than Agroup(P>0.05),B14group(6.96±0.22)and B28 group(8.36±0.27)were higher significantly than Agroup(P<0.01).C7group(2.30±0.32)was not significantly change than B7group,Agroup(P>0.05),C14group(5.16±0.18)andC28(7.02±0.19)were higher significantly than Agroup(P<0.01),but was lower significantly than that of B group at the corresponding time point(P<0.05).D7group(2.27±0.33)was not significantly changethan C7group B7group,Agroup(P>0.05),D14group(4.62±0.19)and D28group(5.93±0.25)were higher significantly than Agroup(P<0.05),but was lower significantly than that of B group and C group at the corresponding time point(P<0.05). E7 group(2.20±0.30)was not significantly changethan D7group,C7group,B7group,Agroup(P>0.05), E14 group(4.16±0.17)and E28 group(4.22±0.23)were higher significantly than A group(P<0.05),but was lower significantly than that of B group,Cgroup and D group at the corresponding time poin(tP<0.05 or P<0.01).3 The activity of SOD in lung tissue (U/mg prot):The SOD activity of B7group(44.34±5.07)was lower significantly than that of A group(78.83±4.77)(P<0.01),after that the activity increased a little, The SOD activity of B14group(58.62±3.98)were still lower significantly than A group(P<0.01),B28 group(72.44±5.16)was not statistic different from A group significantly(P>0.05).C7group(55.12±3.42)were higher significantly than B7group(P<0.05),but was lower significantly than A group(P<0.01),C14 group(66.33±4.15)was lower significantly than A group(P<0.05),but was not statistic higher significantly than B14group(P>0.05),The SOD activity of C28 group (71.18±5.21)maintain higher level,there were not statistic different from A group and B28 group significantly(P>0.05). D7 group(65.78±3.47)were higher significantly than B7group and C7 group(P<0.05),but was lower significantly than A group(P<0.05),D14group(66.91±3.52)was lower significantly than A group ( P<0.05 ), but was not statistic higher significantly than B14group and C14 group(P>0.05),D28 group(70.85±5.06)were not statistic different from A group and B28 group,C28 group significantly(P>0.05). E7group(69.49±3.53)was lower significantly than A group(P<0.05),but were higher significantly than B7group and C7 group,D7group(P<0.01 or P<0.05),E14group(69.58±4.12)was lower significantly than A group(P<0.05)and was higher significantly than B14group(P<0.05),It was higher than C14 group,D14group,but there were no statistic differe(P>0.05),E28 group(73.38±5.88)maintain higher level,there were not statistic different from A group and B28 group,C28group, D28 group significantly(P>0.05).4 The content of MDA in lung tissue(nmol/mg prot): The MDA content of A group were(1.02±0.16).B7group (2.1±0.18)and B14group(1.32±0.19)were higher significantly than A group(P<0.05),B28group(1.24±0.28)was higher than A group but there were no statistic differe (P>0.05).C7group (1.34±0.11) were higher significantly than A group(P<0.05),but were lower significantly than B7 group(P<0.05),C14group(1.24±0.25)and C28group(1.22±0.29)were higher than A group and were lower than Bgroup at the corresponding time point , but there were no statistic differe(P>0.05). D7group(1.28±0.15)were higher significantly than A group(P<0.05)and were lower significantly than B7 group(P<0.05),but it was not lower significantly than C7 group(P>0.05),D14group(1.10±0.23)and D28group(1.09±0.27)were higher than A group and were lower than B group,C groupat the corresponding time point,but there were no statistic differe(P>0.05). E7group(1.30±0.20)were higher significantly than A group ( P<0.05 ) and were lower significantly than B7 group(P<0.05),It were lower than C7group and were higher than D7group,but there were no statistic differe(P>0.05). E14group(1.19±0.27) and E28group(1.11±0.24)were no statistic differe from A group and Bgroup,Cgroup,Dgroup at the corresponding time point(P>0.05).5 The content of MPO in lung tissue (u/g prot): TheMPO content of A group were(5.67±0.26).B7 group(12.63±0.22)and B14 group(10.10±0.21)were higher significantly than A group ( P<0.01 ), B28 group ( 7.16±0.28 ) was higher significantly than A group(P<0.05). C7group (8.25±0.19) were higher significantly than A group(P<0.01)and were lower significantly than B7 group(P<0.05),C14 group(6.87±0.18)were higher significantly than A group(P<0.05)and were lower significantly than B14 group(P<0.05),C28group(6.29±0.29)were higher than A group and were lower than B28 group,but there were no statistic differe (P>0.05). D7group(7.42±0.23)were higher significantly than A group(P<0.05),but were lower significantly than B7 group(P<0.05),It were lower than C7group, but there were no statistic differe(P>0.05). D14group(6.9±0.20)were higher significantly than A group ( P<0.05 ), but were lower significantly than B14 group(P<0.05),D28group(6.35±0.42)were no statistic differe from A group and B28group,C28group(P>0.05).E7 group(7.11±0.13)were higher significantly than A group ( P<0.05 ), but were lower significantly than B7 group and C7 group(P<0.05),It were lower than D7group, but there were no statistic differe (P>0.05),E14group(6.06±0.37)and E28group(6.22±0.38)were no statistic differe from A group and Bgroup,Cgroup,Dgroup at the corresponding time point(P>0.05).6 The change of pathomorphology of lung:The lung tissues of each group display the pathological process of alveolitis and fibrosis,these pathological changes proved the PF rat models induced by bleomycin was successfully duplicated .The degree of alveolitis and fibrosis of Cgroup were alleviated compared to that of corresponding B group significantly(P<0.05),The lung fibrosis of C28 group were significantly alleviated compared to that of B28 group(P<0.05),The degree of alveolitis and fibrosis of Dgroup were alleviated compared to that of corresponding C group significantly(P<0.05),The lung fibrosis of D28 group were significantly alleviated compared to that of C28 group(P<0.05),D group were not statistic different from E group .Conclusion: 1. The unbalace of oxidation-antioxidation system play a important role in the process of lung fibrosis in rats. 2. Aminoguanidine and Erdosteine both can cure Bleomycin-induced pulmonary fibrosis of rats And the therapeutic effect surpass traditional Glucocorticoid treatment ,Moreover Aminoguanidine and Erdosteine play joint action in the process of lung fibrosis . 3. The possible underlining mechanisms that Aminoguanidine and Erdosteine both can cure Bleomycin-induced pulmonary fibrosis of rats are to balace oxidation-antioxidation system by ruduce free radical production and increase free radical remove ; to alleviate lipid peroxidation damage ;to decrease neutrophile accumulation.
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