Role of LY2109761 in radiation-induced pulmonary fibrosis in mice / 中华放射医学与防护杂志

ABSTRACT

Objective To investigate the protective effects and mechanism of LY2109761 in radiation-induced pulmonary fibrosis (RIPF), and to provide a clue for the clinical treatment of RIPF. Methods A total of 40 healthy female C57BL/6 mice were enrolled and were divided into 4 groups with 10 mice in each group randomly, including blank control group, single irradiation group, irradiation +LY50 group and irradiation + LY100 group which were given 50 and 100 mg/kg of LY2109761 respectively, twice per day. The whole lungs were irradiated by 6 MV X-rays of 12 Gy. At 2 weeks post-irradiation, pathological analyses were performed for each group to evaluate the histological changes in the irradiated lungs, including hematoxylin and eosin staining ( HE ) to observe morphologic changes, the Masson staining to estimate the degree of fibrosis and a combination of immunohistochemistry to analyze the expression levels of TGF-β1 and Smad2. Results Compared with control group, the degree of fibrosis of the lung including alveolar structure changes, fibroblast proliferation and alveolar spacing was significantly enhanced at 14 d post-irradiation. Compared with irradiation group, the fibrosis degree in irradiation +LY100 group was significantly reduced(t=4. 668,P<0. 05). The degree of inflammation and fibrosis of the lung in irradiation+LY50 didn′t obviously reduce compared with irradiation group ( P>0. 05 ) . The result of immunohistochemical assay showed that, the level of protein expressions of TGF-β1 and Smad2 was increased significantly after irradiation(t =13. 545, 6. 418, P <0. 05), and obviously decreased in irradiation+LY100 group (t=15. 263, 6. 855, P<0. 05), but just slightly reduced in irradiation+LY50 group (P>0. 05). Conclusions LY2109761 has protective effect in radiation pulmonary fibrosis possibly by down regulating the expressions of TGF-β1/Smad2.