Protective effect and mechanism of ophiopogonin D on radiation-induced lung injury in mice / 中华放射医学与防护杂志

ABSTRACT

Objective:To investigate the protective effect and mechanism of ophiopogonin D on lung injury induced by radiation in mice.Methods:A total of 60 female C57BL/6 mice were randomly divided into 4 groups control group, irradiation group, irradiation+ ophiopogonin D group and irradiation+ dexamethasone group, with 15 mice in each group. The mice were irradiated with a single dose of 6 MV X-rays of 15 Gy. Three days before irradiation, the mice in irradiation+ ophiopogonin D group were intraperitoneally injected with 10 mg/kg ophiopogonin D solution. The mice in irradiation+ dexamethasone group were intraperitoneally injected with 10 mg/kg dexamethasone solution. The mice in control group and irradiation group were intraperitoneally injected with normal saline once a day until 1 week after irradiation. Tissue samples were collected at 3 d, 1 week, and 6 weeks post-irradiation. Hematoxylin-eosin (HE) staining and Masson′s trichrome staining were used to observe the pathological changes of lung tissue. The expressions of 8-hydroxy-deoxyguanosine (8-OHdG), p53, p53 up-regulated apoptosis factor (PUMA), cysteine aspartate proteolytic enzyme-3 (caspase-3), Collagen Ⅰ and Collagen Ⅲ were observed by immunohistochemistry. Western blot was used to verify the expressions of apoptosis related proteins including p53, PUMA and caspase-3.Results:HE staining of lung tissue showed that ophiopogonin D could reduce hemorrhage, exudation, edema and inflammatory infiltration in lung tissue 1 week post irradiation. Moreover, ophiopogonin D reduced the expression of 8-OHdG ( t=8.39, P < 0.05), the oxidative stress, and the expressions of p53, PUMA, caspase-3 apoptosis-related proteins ( t=12.60, 5.92, 7.00, P < 0.05), and inhibited the apoptosis of alveolar epithelial cells and alleviated other damage in the irradiated lung tissue 1 week post-irradiation. Ophiopogonin D also reduced collagen deposition in lung tissue 6 weeks after irradiation, and reduced the expression of transforming growth factor (TGF-β1) ( t=9.32, 8.97, 6.83, P < 0.05) and interleukin-6 ( t=8.22, 7.80, 8.28, P < 0.05) in the blood of mice at 3 d, 1 week, and 6 weeks after irradiation. At 6 weeks after exposure, ophiopogonin D reduced the production of Collagen Ⅰ and Collagen Ⅲ in the lung interstitium ( t=6.41, 7.50, P < 0.05), and alleviated the pulmonary fibrosis in the late stage of radiation. Conclusions:Ophiopogonin D has protective effects on lung injury caused by radiation, including the alleviation of early radiation pneumonia and late pulmonary fibrosis, by reducing oxidative stress, the expression of inflammation-related factors, apoptosis of lung tissue, and collagen production.