Dynamic Expression Of IL-1β And IL-1β Type Ⅰ Receptor In The Rats Of Bleomycin-induced Pulmonary Fibrosis

Background:Pulmonary fibrosis is one of the common clinical pathological changes, it is the common outcome of a variety of interstitial lung diseases unknown causes, and it always causes pulmonary dysfunction and respiratory failure, and its incidence shows an increasing trend in recent years. As the mechanism is unclear, there's still short of effective instrument for the therapy of pulmonary fibrosis today, the mortality is so high and the prognosis is so weak, therefore, strengthen its research on the pathogenesis, and develop new treatment strategies on this basis has become a more urgent and practical need. At present, many experts at home and abroad believe that:the inflammatory cell and multiple cytokine they released play a very important part in the pathogenesis of pulmonary fibrosis. IL-1βis one of the strongest pro-inflammatory cytokines in vivo, it involved in the occurrence and development of many diseases. Studies have reported that:in the animal of pulmonary fibrosis and the patient of idiopathic pulmonary interstitial fibrosis, the content of IL-1βin the BALF was so high. Yet how IL-1βand its receptor changes in the process of pulmonary fibrosis is unknown. Here we establish the animal model of pulmonary fibrosis to investigate the variation of IL-1βand its receptor in the process of pulmonary fibrosis, so as to further explore the mechanism of pulmonary fibrosis and provide a new theoretical basis for the clinical treatment.Objective 1.To investigate the lung tissue pathological changes in the rats of pulmonary fibrosis.2.Test the content of hydroxyproline in the lung tissue3.Watch the changes of IL-1βand IL-1RI in the lung tissue,the serum and BALF in rats of pulmonary fibrosisMethods 90 rats were randomly divided into the normal group(N-group, n=30), the model group(M-group, n=30)and the methylprednisolone group (Met-group, n=30). The pulmonary fibrosis model was established by intratracheal injection of bleomycin with rats of the M-group and Met-group; while rats of the N-group injected with distilled water. From the day on, rats of the Met-group were injected with methylprednisolone sodium phosphate in intraperitoneal every day, those of the N-group and M-group were injected with saline. The animals were killed on the 1st,3rd,7th,14th, and 28th days after treatment, each six rats each group.Hold the lung tissue, stain it with HE, investigate the lung tissue pathological changes and assay the content of hydroxyproline in them using the alkaline solution. Detect the contents of IL-1βand its typeⅠreceptor in the lung tissue by using the method of immunohistochemistry. Collect the bronchoalveolar lavage fluid(BALF) and the blood serum, test the contents of IL-1B and its type I receptor in them using Enzyme-linked immunosorbent assay (ELISA).Results 1.Pathological evidence of the M-group rats demonstrated that the alveolar compartment companied with massive inflammatory cell invasion and a number of myofibroblast proliferation became more thick. However, lung injury in the Met-group rats got better than that in the M-group.2.The content of hydroxyproline was increasing as time goes, and achieved peak on the 28th day both in M-group and Met-group, but that of the M-group was significantly higher than that of the N-group(P<0.01), and the Met-group was significantly lower than the M-group (P<0.01).3.Immunohistochemistry results show:IL-1βand IL-1RI in lung tissues in model-group shows a highest expression scoring on the 3rd, and reduced on the 14th day, and equal to the normal-group almost on the 28th day. The expression scoring of IL-1βand its type I receptor in Met-group were smaller than that in M-group on the 3rd,7th and 14th day.4.The results of ELISA:IL-1βin BALF and blood serum achieved peak on the 7th day in M-group, which decreased markedly on the 14th day, but also significantly higher than that of the N-group(P<0.01), and down to the normal level almost on the 28th day. While the expression pattern of IL-1RI was almost similar to that of IL-1β.The contents of IL-1βand its type I receptor in Met-group were lower than M-group on 3rd,7th and 14th, (P<0.01).Conclusion The content of IL-1βand the type I receptor for IL-1βwere increasing in the stage of alveilitis obviously and decreasing significantly in the period of fibrosis. They show a regular pattern of rising to the peak early and briefly in pulmonary fibrosis. It implies that they play an important role in the earlier period of pulmonary fibrosis.