Establishment and validation of radiation-induced heart fibrosis on SD rat model

Abstract

Objective To establish a Sprague-Dawley (SD) rat model of radiation-induced heart injury and myocardial fibrosis. Methods Using the small animal radiation research platform, 18-Gy radiation was given to the heart of male SD rats in a single fraction. At six months after radiation, heart structure and function were assessed by color Doppler ultrasound; heart injury and collagen fiber deposition were evaluated using HE staining and picrosirius red staining, respectively; heart collagen content was analyzed by hydroxyproline measurement. Results According to the color Doppler ultrasound assessment, the left ventricular posterior wall thickness during systole was significantly smaller in the radiation group than in the control group (0.22±0.01 vs. 0.25±0.05 cm, P=0.037). The results of picrosirius red staining showed that the proportions of fibrosis area in the right ventricle, interventricular septum, and left ventricle were significantly higher in the radiation group than in the control group ((2.99±1.29)% vs. (2.21±0.87)%, P=0.025; (2.53±1.27)% vs. (0.91±0.70)%, P=0.000; (2.45±1.98)% vs. (0.54±0.31)%, P=0.000). According to the measurement of hydroxyproline concentration, the radiation group had a significantly higher level of hydroxyproline than the control group (0.56±0.02 vs. 0.49±0.05 ug/mg, P=0.010), indicating severe heart collagen deposition after radiation. Conclusions At the end of model establishment, SD rats have obvious myocardial fibrosis and reduced left ventricular posterior wall thickness during systole, suggesting that a SD rat model of radiation-induced heart injury and myocardial fibrosis is successfully established. Key words: Radiation-induced myocardium fibrosis; Animal model; Rat