Effects and mechanism of hyperin against bleomycin-induced pulmonary fibrosis in mice

  Objective  To investigate intervention effect and mechanism of hyperoside on bleomycin-induced pulmonary fibrosis in mice.

  Methods  Totally 36 male C57BL/6 mice were assigned randomly into a control group (normal saline), a model group, and low, moderate, and high hyperoside-dosed groups (25, 50, and 100 mg/kg) and a prednisone group. Mice pulmonary fibrosis model was constructed with administration of bleomycin through intra-tracheal instillation continuously for 28 days and then the mice were sacrificed. The pulmonary tissues were stained with hematoxylin-eosin (HE) and Massonn′s method. The expressions of collagen I and collagen II in pulmonary tissues was determined immunohistochemically; while the content of hydroxyproline (HYP) wherein was measured with a reagent kit. The content of transforming growth factor-β1 (TGF-β1) in serum and the level of interleukin-6 (IL-6) in bronchoalveolar lavage fluid were also measured.

  Results  The body weight of mice in the model group was reduced significantly compared to the control group; whereas that of the hyperoside-dosed groups was increased significantly compared to the model group (both P < 0.05). The score of pulmonary alveolitis and fibrosis of the model group (2.83 ± 0.41 and 2.83 ± 0.41) were increased markedly compared to those of the control group (both P < 0.05); whereas, the scores in the hyperoside-dosed groups and prednisone group were reduced profoundly compared to those of the model group (P < 0.05 for all). Significantly decreased scores of pulmonary alveolitis (1.00 ± 1.10, 1.67 ± 1.03, and 1.50 ± 1.05) and pulmonary fibrosis (1.00 ± 0.63, 1.33 ± 1.03, and 1.83 ± 0.75) were observed for the mice of the high, moderate hyperoside-dosed group and the prednisone group compared to the mice of the model group (P < 0.05 for all) . The expressions of collagen I, collagen Ⅲ, and HYP content in the pulmonary tissues of the model group were increased significantly compared to those of the control group; whereas the expressions in the high hyperoside-dosed group and prednisone group were significantly reduced compared to those of the model group. Both the serum TGF-β1 (182.83 ± 11.15 pg/mL) and IL-6 in bronchoalveolar lavage fluid (89.36 ± 7.21 μg/mL) were increased significantly for the model group compared to those of the control group (P < 0.05 for all); whereas, the TGF-β1 and IL-6 were markedly reduced for the high and moderate hyperoside-dosed groups compared to the model group. Significantly decreased serum TGF-β1 (121.37 ± 8.25, 135.78 ± 17.29, and 112.73 ± 10.23 pg/mL) and IL-6 in bronchoalveolar lavage fluid (48.25 ± 8.39, 71.90 ± 7.74, and 44.45 ± 7.15 μg/mL) were detected in the high, moderate hyperoside-dosed groups and prednisone group compared to those in the model group (P < 0.05 for all).

  Conclusion  Hyperoside can effectively alleviate bleomycin-induced pulmonary fibrosis in mice. The underlying mechanism my be the hyperoside-related inhibition of collagen secretion and inflammation response.