Effects of valsartan on bleomycin-induced pulmonary fibrosis in rats and the expression of hepatocyte growth factor in lung tissue

Objective To study the effect of valsartan on bleomycin-induced pulmonary fibrosis in rats and its possible mechanism. Methods Sixty Wistar rats were divided into three groups. In the valsartan group and the model groups, pulmonary fibrosis was induced by intratracheal instillation of bleomycin(BLM), and then the former group reveived valsartan 16 mg/kg daily, but the latter group received oral normal saline. In the control group, normal saline was given both intratracheally and orally. Five rats in each group were sacrificed 7,14,28,and 42 days after intratrachel instillation. Collagen content of the lung tissue was assessed by hydroxyproline concentration. Histological changes of the lungs were evaluated by HE stain and Masson′s trichrome stain. Lung expression of transforming growth factor-β (TGF-β) protein was assessed by immunohistochemistry. The mRNA of hepatocyte growth factor (HGF) was detected by in situ hybridization, and the level of HGF protein was further measured by ELISA. Results In the valsartan group, alveolitis [(0.88±0.12)points,(0.79±0.21)points, (0.75±0.17)points] decreased significantly 14 days after treatment with BLM and was significantly lower as compared with the model group[(2.05±0.25)points, (1.38±0.12)points, (1.19±0.11)points, P0.01]. Pulmonary fibrosis on day 7,28,42[(0.28±0.03)points vs(0.45±0.10)points, (1.74±0.18)points vs( 2.08±0.32)points, (1.91±0.09)points vs(2.77±0.15)points, P0.05], hydroxyproline concentrations on day 14,42[(1.08±0.13)μg/mg·pro vs(1.45±0.19)μg/mg·pro,(1.39±0.20)μg/mg·pro vs(2.19±0.37)μg/mg·pro, P0.01] and protein expession of TGF-β on day 7,42[2.27±0.30 vs 3.99±0.43, 2.05±0.18 vs 2.71±0.46, P0.05] in the valsartan group all reduced significantly as compared with that of the model group. HGF mRNA [1.61±0.20 vs 1.98±0.23,0.52±0.19 vs 0.28±0.14,P0.05] and its protein expression(204±18)pg/ml vs (260±21) pg/ml,(129±20)pg/ml vs (100±20)pg/ml,P0.05) on day 7 and day 42 in the valsartan group were increased as compared with those of the model group. Conclusions Valsartan alleviates BLM-induced pulmonary fibrosis in rats. Inhibiting the expressions of TGF-β and stimulating the expression of HGF in lung tissues may be one of the mechanisms.