Effect Of Halofuginone In The Prevention Of Radiation Induced Lung Injury

Objective:To investigate the effects of halofuginone on inhibition of pulmonary injury induced by irradiation and try to explore the mechanismas.Methods:Sixty C57BL/6J mice were randomly divided into4groups:12in control group, without any treatment;18in irradiation group, X-ray irradiaton with12Gy/f x If;12in halofuginone group, with halofuginone gavage administration as in combination group;18in combination group, with halofuginone gavage administration of25μg daily for each mouse for30days, and irradiation was given as in the irradiation group. At24hour,1,2,4,12,20weeks after irradiation, two mice in control/halofuginone group and three mice in irradiation/combinaton group were randomly sacrificed, and total lung were harvested. The left lung was fixed to make pathological sections which were stained with HE, and were stained with immunohistochemical technique. The right lung was cryopreserved to measure the level of hydroxyproline.Results:HE staining showed that, for the irradiation group, alveolar inflammation occurred at24hour after irradiation and the inflammation were still significant at one week after irradiation. At two weeks after rradiation, alveolar inflammation decreased and the alveolar walls and alveolar interstitial began to thicken. At four weeks after irradiation, the alveolar walls and alveolar interstitial became thickened significantly. The alveolar distended and the fibrosis was shown at12weeks after irradiation. A part of alveolar was closed and the fibrosis was significant at20weeks after irradiaton. For the combination group, inflammation and fibrosis ameliorated significantly. There were no significant differences between the control group and halofuginone group. Immunohistochemical method showed that the level of TGF-β1in irradiation group and combination group were increased after irradiation and reached to the highest level at the second week after irradiation. The level of TGF-β1in halofuginone group were higher than that in combination group at different time points (P=0.083、0.129、0.026、0.032、.201、0.037), and the differences were significant at two weeks after irradiation. Control group and halofuginine group had a very low expression of TGF-β1, and there were no significant differences between them(P>0.1). The level of hydroxyproline in irradiation group and hafuginone group were increased after irradiation and there were no significant change at the other goups. At20weeks after irradiation, irradiation group had a significant higher level of hydroxyproline than combination group (P=0.037).Conclusion:Halofuginone might ameliorate irradiation induced lung inflammation and fibrosis, inhibit TGF-β1expression and decrease the level of hydroxyproline. Therefore, halofugione is expected to be a therapeutic drug to prevent irradiation induced pulmonary injury.