Thalidomide suppresses bleomycin-induced pulmonary fibrosis by down-regulating expressions of TGF-β_1 and TNF-α in rats

Objective To investigate the effects of Thalidomide on bleomycin-induced pulmonary fibrosis in rats and to study the possible mechanism. Methods Forty-five healthy male wistar rats were randomized into three groups: normal control group (group N) , pulmonary fibrosis model group (group M) and thalidomide group (group T), with 15 rats in each group. The group M received intra-tracheal instillation of 5 mg/kg bleomycin (BLM) for modeling of pulmonary fibrosis, and intraperitoneal injection with daily DMSO on the next day; group T received BLM in the same, and intraperitoneal injection with 4 mg Thalidomide (dissolved in DMSO); group N was injected intraperitoneally with DMSO after intratracheal instillation of saline. Every five rats in each group were sacrificed at random for pathological sections of lung on days 7, 14 and 28 after modeling, respectively. The degree of pulmonary alveolitis and pulmonary fibrosis was evaluated by staining with HE and trichrome masson staining. The level of hydroxyproline (Hyp) in the lung tissue was examined by alkaline hydrolysis, and the levels of TGF-β1 and TNF-α in BLAF measured with double antibody sandwich ELISA. Results In group M, pulmonary fibrosis increased gradually and became significant on day 28, with higher scores of alveolitis and fibrosis, and higher levels of Hyp, TGF-β1 and TNF-α compared with those in group N(P0.05). Group T showed significantly less fibrosis than group M at all time points (P0.05), and compared with group M, the score of pulmonary fibrosis and level of Hyp were apparently lowered on days 14 and 28 (P0.05). Moreover, the levels of TGF-β1 and TNF-α in BALF in group T were also significantly lower than those in group M (P0.05). Conclusion Thalidomide may alleviate the degree of bleomycin-induced pulmonary fibrosis in rats by down-regulating the expressions of TGF-β1 and TNF-α in the lungs.