| Objective:Interstitial lung disease (ILD) is regarded as a disease induced by intersitital injury, lesions involving alveolar walls and alveolar surrounding tissues. Idiopathic interstitial pneumonia (IIP) occupy the important position in interstitial lung disease, this is a group of unexplained diffuse lung disease. Idiopathic pulmonary fibrosis (IPF) is a kind of Idiopathic interstitial pneumonia, histopathological performance for unusual type interstitial pneumonia, a chronic progressive development of the disease. The disease pathology characteristic performance for inflammation response, fiber cell proliferation and extracellular matrix protein deposits..Research has shown that in pulmonary fibrosis form process there are a type1auxiliary T cells and type2auxiliary T cells of the imbalance between factors, namely TH1/TH2immune imbalance.INF-y belongs toTHl cells factor, have the function of the anti fibrosis, mainly by inhibiting into fiber cell hyperplasia, restrain collagen deposition, restrain TGF-produces and the activation, and promote the degradation of fibroblasts aspects to fulfill. IL-4are TH2cytokines type. IL-4can enlarge inflammatory reaction, cause lung heavy model of the structure, stimulate the lungs into fiber cell hyperplasia, and adjust the fibroblasts chemotactic, proliferation, collagen synthesis, and collagen and cellulose sedimentary increased, cause alveolar walls the thickened basement membrane and diffuse epithelial next fibrosis. Studies have found that as mediators17interleukin (IL-17) involved in the pathogenesis of pulmonary fibrosis.Current therapy usually includes corticosteroids with or without a cytotoxic agent. But the effects of the immunosuppressive therapy are limited, and the adverse effects cannot be ignored Currently, new potential antifibrotic therapies are under investigation, but effective treatment is currently lacking. Overseas for azithromycin treatment pulmonary fibrosis do more thorough research, and display can reduce pulmonary fibrosis degree of improving lung functionThe main purpose of this study is to research the effect of azithromycin on bleomycin-induced pulmonary fibrosis in rat. By detecting the contents of hypdroxyproline (HYP) in lung tissue, the expression level of the laage IL-4, INF-y, IL-17levels of influence, and compare with dexamethasone, discussed the mechanism of azithromycin anti fibrosis and effect.Method:90healthy male Sprague-Dawley (SD) rats (provided by Center Experiment Animal of Hebei Medical University) weighting220±10g were randomly divided into three groups after one week feeding.1) Control group (group A):30rats. They were injected about normal saline (0.1ml/100g) in trachea, and were given intragastric administration with normal saline (1ml/100g) once a time per day after fake establishing model, then were killed randomly on the7th day, the14th day and the28th day (n=10, at each time point).2) Model group (group B):30rats. Pumlonary fibrosis was induced by intratracheal injection of Bleomycin A5(5mg/kg). They were given intragastric administration with normal saline (1ml/100g) once a time per day after establishing model, then were killed randomly on the7th day (n=9), the14th day (n=10) and the28th day (n=9).3) Azithromycin group (group C):30rats. They were injected Bleomycin A5(5mg/kg) in trachea, and were treated with azithromycin solution (25mg of thalidomide dissolved in100ml of normal saline)5mg/kg once a time per day after establishing model, then were killed randomly on the7th day (n=9), the14th day (n=10) and the28th day(n=10).4) Dexamechasone group (group D):30rats. They were injected Bleomycin A5(5mg/kg) in trachea, and were treated with dexamechasone solution (3mg/kg) once a time per day after establishing model, then were killed randomly on the7th day (n=10), the14th day (n=10) and the28th day(n=9). Each cut right femoral artery bleed to death, after death instantly line laage and collect laage fluid. The content of IL-4, IL-17and INF-γ in laage fluid were detected by the method of ELISA (enzyme linked immunosorbent assay). Estimate the degree of alveolitis and pulmonary fibrosis by HE staining, Masson staining and divide by the method of Szapiel into4grades. The superior lobes of right lung were made into homogenate to evaluate the concentration of HYP in lung tissue. Statistics work was done with SPSS13.0statistical software.Results:1The results of pulmonary pathology:The level of alveolitis of group B was more serious than that in group A on each time point (P<0.01). The level of fibrosis in group B was more serious than that in group A on the7th day, the14th day and the28th day(P<0.01). These indicate that the model of pulmonary fibrosis estabished successfully. The levels of alveolitis and fibrosis in group C were less serious than that in group B. The levels of alveolitis in group C were less serious than that in group B on the7th day (P<0.01). The levels of alveolitis and fibrosis in group C were less serious than that in group B on the14th day(P<0.01). The levels of fibrosis in group C were less serious than that in group B on the28th day (P<0.01). The levels of alveolitis and fibrosis in group D were less serious than that in group B. The levels of alveolitis in group D were less serious than that in group B on the7th day (P<0.01). The levels of alveolitis and fibrosis in group D were less serious than that in group B on the14th day(P<0.01). The levels of fibrosis in group D were less serious than that in group B on the28th day (P<0.01). Group C and D group alveolar inflammation and fibrosis difference in the degree was not statistically significant.2The change of the content of HYP in lung tissue:The content of HYP in group B shown an increase tendency accompany with the time and reached a peak on the28th day. Compared with group A, there were significant difference on each time point (P<0.01). The values of HYP of the rats in group C and D were also increased, but took on a low level. The values of HYP in group C and D were all lower than that in group B on the7th day, the14th day and the28th day (P<0.01). Group C and D rats HYP difference in content was not statistically significant.3The change of the content of INF-y in bronchoalveolar lavage:The expression of INF-γ in evey group on each time points were no statistically significant difference in comparison with each another.4The change of the content of IL-4and IL-17in bronchoalveolar lavage:The expression of IL-4and IL-17in group B was significantly higher than that in group A, group C and group D on each time point. There were statistical significance on the7th day and the14th day and the28th day (P<0.01). The expression of IL-4and IL-17in group A, C and D were no statistically significant difference in comparison with each another.Conclusions:1Azithromycin can reduce collagen deposition in pulmonary interstitium and possesses some therapeutic effect in bleomycin-induced pulmonary fibrosis models in rat. Azithromycin is similar with dexamethasone of anti-fibrosis and fewer side effects.2There is a imbalance between TH1cells factor IL-4and TH2cell factor INF-γ in bleomycin-induced pulmonary fibrosis models in rat. Azithromycin can correct this imbalance by a certain degree, and to lessen the early inflammatory reaction, reduce late fibrosis change, this could be potential mechanism of azithromycin against pulmonary fibrosis.3There were TH17cell factor IL-17significantly increased in rats pulmonary model group. This indicated that the TH17cell may be involved in the process of pulmonary fibrosis. Azithromycin can significantly reduce the increase of IL-17. Adjusting IL-17expression may be another mechanism of azitohromycin reducing pulmonary fibrosis. |
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