The Effect Of Inhaled Budesonide On The Expression Of MMP-2 And TIMP-2 In Lung Tissue Of Pulmonary Fibrosis Rats

Objective:To investigate the effect of inhaled budesonide(Bud) on the expression of matix of metalloproteinases-2(MMP-2) and tissue inhibitors of metalloproteinases-2(TIMP-2) in lung tissue of bleomycin (BLM)- induced rat pulmonary fibrosis,and to discuss the possible mechanism. Methods:Forty-five Wistar rats were randomly divided into the Bud group,the BLM group and the NS group. The Bud group and the BLM group were intratracheally instilled with BLM to induce pulmonary fibrosis,while the NS group with NS in the same condition.The Bud group were aerosolized with Bud on the 1-6th day,while the other two groups with NS.Five rats in each group were randomly killed on the 7th,14th and 28th day,and the lung tissue samples were harvested. HE and Massion staining were used to dertermine the extent of alveolitis and fibrosis.At the same time immunohistochemical staining was used to detect the expression levels of MMP-2 and TIMP-2 in lung tissues. Results: The extent of alveolitis and pulmonary fibrosis in BLM group on 7th,14th,28th day were significantly higher than those of NS group (P<0.5); The extent of alveolitis in Bud group on 7th,14th day were lower than those of BLM group (P<0.05); The extent of pulmonary fibrosis in Bud group on 7th,14th ,28th day were lower than those of BLM group (P<0.05); The levels of MMP-2 and TIMP-2 in BLM group on 7th,14th,28th day were significantly higher than those of NS group(p<0.5);The levels of MMP-2 and TIMP-2 in Bud group on 7th,14th,28th day wre lower than those of BLM group (P<0.05),and the ratio of MMP-2/TIMP-2 in Bud group on the 28th were higher than those of BLM group.Conclusion: 1.The levels of MMP-2 and TIMP-2 in Bud group and BLM group were higher than those of the NS group.These results suggested that MMP-2 and TIMP-2 could cause lung injury and pulmonary fibrosis in the early day of pulmonary fibrosis (on the 7th).Increased the levels of MMP-2, enhanced the roles of degradation, and caused lung injury. However, the levels of TIMP-2 also increased, the ratio of MMP-2/TIMP-2 were still balance.Hence,these was no extracellular matrix (ECM) accumulation in the early day.In the lattter day,the levels of MMP-2 reduced,but the levels of TIMP-2 increased, and the ratio of MMP-2/TIMP-2 decreased, which could cause ECM deposion and pulmonary fibrosis. 2. The inhaled Bud could reduce the levels of MMP-2 and TIMP-2 in lung tissues and regulate the balance of MMP-2 and TIMP-2,and delay or even inhibit the process of pulmonary fibrosis. The possible mechamism is that Bud had a strong anti-inflammatory effect. It could decrease much cytokines such as interleukin -1 (IL-1), tumor necrosis factor (TNF-a), epidermal growth factor (EGF), etc. which could reduce MMP-2 and TIMP-2 expression.