The Initial Research Of Establishing Chronic Radiation-induced Lung Injury Model

Objective: Lung injury is an acute or chronic injury course caused by many pathogenic factors inside and outside the lung, the establishment and application of animal model play an important role in the research of pathogenesis and pathophysiology of lung injury. The lung-injured animal model is made by the bleomycin, however, it is simple and feasible, but its mechanism of lung-injury is different from the irradiation one, so there may be some conflicting conclusions. In order to compare the pathological difference between bleomycin lung-injured and irradiation one accurately, we use New Zealand white rabbits to establish two kinds of the models, observe and analysis the different characters through CT and pathology, provide a new animal lung-injured model, probe the possibility of establishment the chronic radiation-induced lung injury models according to the clinical methods.Methods: 40 rabbits were divided into four groups, the bleomycin one, the right whole lung irradiation one, the whole lung irradiation one and the blank control one at random. The animal in the bleomycin group were injected with bleomycin through trachea. The irradiation groups were irradiated according to the SAD fixed angle irradiation technology, the dose in the right whole lung group and the whole lung group is 40GY and 30GY respectively, the single dose given is based on the radiation dose formula. The animals were given CT and pathology examination after 1, 2, 4, 8, 12 and 16 weeks.Results: There were deaths in the irradiation groups in the first four weeks, but no deaths happened in the bleomycin group. The irradiation lung injury appeared early with a high incidence in the right whole irradiation, it is acute radiation pneumonitis through the CT and pathology examination. 8-12weeks after the irradiation, there were the ground glass signs, patchy and fiber cord in the CT exhibition and the alveolar thickened with fibrosis. The lung injury in bleomycin group happened after injection in the following 2 weeks, there were shadows and fibrosis cord changes through CT, the bullae formation and local fibrosis were observed around the main bronchi and vessels. After 4-12 weeks, there were extensive lung fibrosis, bullae formation and the part of atelectasis.Conclusion: Using New Zealand white rabbits, it is feasible and safe to establish the chronic radiation-induced lung injury model according to the SAD irradiation technology. Moreover, with the unilateral lung irradiation dose of 40GY and the bilateral lung dose of 30GY, we can clearly observe the pathological changes of radiation lung injury. There is a great different pathology process between the bleomycin lung injury and irradiation lung injury, the bleomycin model is not suitable to research the irradiation lung injury.