Abstract: Objective To investigate the effects of ulinastatin (UTI) combined with magnesium isoglycyrrhizinate (MgIG) on the expression of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) in lung tis⁃ sue of rats with pulmonary fibrosis induced by bleomycin (BLM). Methods Ninety Wistar rats were randomly divided into five groups: BLM group, methylprednisolone (MTH) group, UTI group, MgIG group and UTI combined with MgIG (UTI + MgIG) group, n=18 for each group. The rat model of pulmonary fibrosis was established by injecting bleomycin through tra⁃ chea in five groups. Twenty-four hours after treatment with BLM， rats were treated with normal saline every day in BLM group, and rats were treated by corresponding drugs in other groups. Six rats of each group were killed at the 7th,14th and 28th day respectively. The pathological changes of alveolitis and pulmonary fibrosis were evaluated by HE staining, and ex⁃ pression levels of TGF-β1 and CTGF in lung tissues were detected by immunohistochemistry method. Results (1) Com⁃ pared with BLM group, the degree of alveolitis and pulmonary fibrosis was reduced in other groups. There was significant dif⁃ ference in alveolitis at the 7th and 14th day between UTI + MgIG group and BLM group. And there was significant difference in pulmonary fibrosis at the 14th and 28th day between UTI + MgIG group and BLM group (P < 0.05). (2) Compared with BLM group, the expression levels of TGF-β1 and CTGF were decreased in other groups. In UTI + MgIG group, the expres⁃ sion levels of TGF-β1 were significantly lower at the 7th and 14th day compared with those in UTI group and MgIG group, and which were significantly lower at the 28th day than those in MTH group, UTI group and MgIG group (P < 0.05). The ex⁃ pression levels of CTGF were significantly lower at the 7th day in UTI + MgIG group than those in UTI group and MgIG group, and which were significantly lower at the 14th and 28th day than those in MTH group, UTI group and MgIG group (P < 0.05). Conclusion The combination of UTI and MgIG can alleviate alveolitis and fibrosis in BLM-induced pulmonary fibrosis rats, which might related with the down-regulation of TGF-β1 and CTGF expressions.

Key words: pulmonary fibrosis, transforming growth factor beta1, rats, Wistar, connective tissue growth factor, ulinastatin, magnesium isoglycyrrhizinate