An Appreciation for the Rabbit Ladderlike Modeling of Radiation-induced Lung Injury with High-energy X-Ray

Background: To evaluate the utility of rabbit ladderlike model of radiation-induced lung injury (RILI) for the future investigation of computed tomography perfusion. Methods: A total of 72 New Zealand rabbits were randomly divided into two groups: 36 rabbits in the test group were administered 25 Gy of single fractionated radiation to the whole lung of unilateral lung; 36 rabbits in the control group were sham-radiated. All rabbits were subsequently sacrificed at 1, 6, 12, 24, 48, 72 h, and 1, 2, 4, 8,1 6, 24 weeks after radiation, and then six specimens were extracted from the upper, middle and lower fields of the bilateral lungs. The pathological changes in these specimens were observed with light and electron microscopy; the expression of tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta 1 (TGF-beta(1)) in local lung tissue was detected by immunohistochemistry. Results: (1) Radiation-induced lung injury occurred in all rabbits in the test group. (2) Expression of TNF-alpha and TGF-beta 1 at 1 h and 48 h after radiation, demonstrated a statistically significant difference between the test and control groups (each P < 0.05). (3) Evaluation by light microscopy demonstrated statistically significant differences between the two groups in the following parameters (each P < 0.05): thickness of alveolar wall, density of pulmonary interstitium area (1 h after radiation), number of fibroblasts and fibrocytes in interstitium (24 h after radiation). The test group metrics also correlated well with the time of postradiation. (4) Evaluation by electron microscopy demonstrated statistically significant differences in the relative amounts of collagen fibers at various time points postradiation in the test group (P < 0.005), with no significant differences in the control group (P > 0.05). At greater than 48 h postradiation the relative amount of collagen fibers in the test groups significantly differ from the control groups (each P < 0.05), correlating well with the time postradiation (r = 0.99318). Conclusions: A consistent and reliable rabbit model of RILI can be generated in gradient using 25 Gy of high-energy X-ray, which can simulate the development and evolution of RILI.