The Effects And Mechanisms Of Celecoxib And Losartan In Bleomycin-induced Pulmonary Fibrosis In Rats

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 become the most important disquisitive aspect that finding the methods of curing IPF, expecilly medication.Objective Observe whether Th1/Th2 unbalance exists in BALF from bleomycin-induced pulmonary fibrosis rats. Study the effects and mechanisms of celecoxib and uintd group of celecoxib and losartan in curing Bleomycin-induced pulmonary fibrosis of rats.Method 48 Sprague-Dawley male rats weighting 250±10g were randomly divided into four groups. (1)Control group: six rats,were injected saline in trachea and oesophagus,and killed at 7th day. (2)BLM group:twelve 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 7^th day and 28^th day(n=6,at each time point)by puncturing heart to obtain blood.(3)Celecoxib group(C group): twelve rats,were injected celecoxib(0.6%,5ml/kg) into oesophagus once a day after lung fibrosis was induced,killed ditto.(4)Celecoxib and Losartan group(CL group): twelve rats, were injected celecoxib(0.6%,5ml/kg) and losartan(10mg/kg) into oesophagus once a day after BLM given,and killed ditto. 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 lavaged by 4℃saline,and then the BALF was centrifuged and took the supernate.The concentrations of IFN-γand IL-4 in BALF in each time point were tested by ELISA.The data was analyzed by SPSS11.5 statistic software.Results 1 Changes of IFN-γlevel in BALF :In BLM group,the concentrations of IFN-γat 7^th day and 28^th day were 15.59±2.05pg/ml,16.99±2.41pg/ml,lower than that of the control group(23.55±3.57pg/ml,P<0.01).In C group,the level of IFN-γat 7^th day(19.17±2.78pg/ml) increased significantly compared with that of BLM group (P<0.05);but the level of IFN-γat 28^th day(16.99±2.41pg/ml) was same as that of BLM group(P>0.05). The concentrations of IFN-γin CL group (CL7d:21.34±1.99 pg/ml, CL28d:22.18±1.95pg/ml) increased, more than those of BLM group (P<0.01), but the level at 7th day in CL group was equal to the C group's.2 Changes of IL-4 level in BALF: The levels of IL-4 in BLM group (BLM7d: 14.64±2.06pg/ml, BLM28d: 13.28±1.42pg/ml) rised compared with that of the control group (9.25±1.81 pg/ml),and showed singinificant difference (P<0.01). In C group,the levels of IL-4 at 7^th day (12.12±2.13pg/ml) and 28^th day (11.01±1.71pg/ml) reduced significantly compared with the BLM groups'(P<0.05).In CL group,the concentrations of IL-4 in BALF (CL7d: 9.55±1.51pg/ml,CL28d: 7.42±1.53pg/ml) decreased significantly compared with the BLM group's(P<0.01) and the C group's (contrast with C28d P<0.01).3 The histopathologic changes :the degrees of alveolitis and lung fibrosis in C group decreased significantly compared with those in BLM groups'(P<0.05).In CL group,those also decreased ,and had significant difference from those in BLM group(P<0.01) and C group (P<0.05).Conclusion 1 The unbalance of Thi/Th2 cytokine exists in Bleomycin -induced pulmonary fibrosis in rats.2 Celecoxib and united group of celecoxib and losartan both can cure Bleomycin-induced pulmonary fibrosis in rats by accommo- dating the unbalance of Th1/Th2,and the latter has a more evident effect.