Preliminary Study On The Protective Effect Of Chloroquine On Radiation-induced Pulmonary Injury In Mice

Objective:To investigate the radioprotective effect of chloroquine (CQ) on thoracic radiation-induced lung injury using mouse model.Methods:In this study, C57BL/6J male mice were thoracically irradiated with 15Gy or 20Gy X-ray to establish radiation-induced pulmonary injury model. The mice exposed to irradiation exhibited decrease of body weight, survival rate and average survival time. Then, the animals were sacrificed at different time points after irradiation and the lung tissue was processed for definitive analysis, including the wet to dry ratio analysis, Malondialdehyde (MDA) content test by UV spectrophotometer, superoxide dismutase (SOD) vitality examination and the interleukin-6 (IL-6) levels of lung bronchoalveolar lavage fluid (BALF) using Enzyme-Linked Immunosorbent Assay (ELISA).Results:1.After a one-time full thoracic irradiation with 20Gy X-ray, weight decreasing and died emerging in each group of mice within 15 days. While after a one-time full thoracic irradiation with 15Gy X-ray, the 30 days survival rate of CQ prophylactic group and CQ therapeutic group were 50% and 62.5%.This results were increased by 16.7% and 29.2% compared with irradiation group. In addition, the average survival time of mice in CQ prophylactic group and CQ therapeutic group were prolonged compared with irradiation group.2.After a one-time full thoracic irradiation with 15Gy X-ray, the MDA content and SOD vitality of lung tissue, the IL-6 levels of BALF changes emerging in each group of mice within 30 days. In the experiment of MDA testing, the MDA content of lung tissue was increased(P<0.01) compared with control group after irradiation. However, it failed to reduce the level of MDA of lung tissue when the mice were given CQ(50mg/kg). As for SOD activity of the mouse lung tissue, it was observed that the differences among the groups had no statistically significant. In addition, the IL-6 levels of BALF was significantly increased(P<0.001) compared with control group after irradiation. While it also significantly reduced (P<0.001) when the mice were given CQ compared with irradiation group.Conclusion:1. The condition that a one-time full thoracic irradiation with 15Gy X-ray was suitable to establish radiation-induced lung injury during a short period time. Treating with CQ before and after irradiation was suited for the mode of administration.2. CQ reduced the level of IL-6 in lung tissues to alleviate lung inflammation reaction, but failed to mitigate radiation-mediated lipid peroxidation lung.In summary, this study demonstrates that CQ has a potential protective effect to radiation-induced lung injury. Mechanically, CQ could decrease the level of lung tissue IL-6 to mitigate lung inflammation reaction.This study provides an important reference for the use of CQ in clinical application and further molecular mechanism study of radioprotector for radiation-induced lung injury.