Radiological Biology
Mechanism of racanisodamine on alleviating radiation-induced lung injury in mice
Guo Haochun, Chen Jiajia, Pu Juan, Ding Zhou, Yu Hanxu, Dong Lei, Zhang Haijun, Wang Wanpeng
Published 2023-06-25
Cite as Chin J Radiol Med Prot, 2023, 43(6): 418-424. DOI: 10.3760/cma.j.cn112271-20230210-00032
Abstract
ObjectiveTo investigate the protective effect of racanisodamine on lung injury in mice exposed to irradiation.
MethodsC57BL/6 mice were randomly divided into control group, racanisodamine group, 18 Gy irradiation group (model group) and racanisodamine combined with 18 Gy irradiation group (treatment group), with 5 mice in each group. The mice in the treatment group received racanisodamine (5 mg/kg) intraperitoneally 3 d before irradiation and contained the whole experiments. Then, single chest irradiation of 18 Gy X-rays was performed both in the model and treatment groups. The racanisodamine group and treatment group received racanisodamine intraperitoneally once a day until 6 weeks after irradiation. The mice were killed at 6 weeks after irradiation. The lung histopathology was observed by HE staining. Serum and bronchial alveolar lavage fluid (BALF) inflammatory cytokines such as TNF-α, IL-1β and IL-6 were determined by ELISA method. Cell senescence was detected by SA-β-Gal staining. The expressions of Nrf2, p-Nrf2 and p62 in lung tissue were performed by immunehistochemistry and Western blot assays.
ResultsCompared with the model group, the scores of HE staining were decreased (t=8.66, P<0.01), the number of infiltrated inflammatory cells in BALF were decreased (t=10.70, P<0.01), and protein concentration in BALF had lower levels (t=6.75, P<0.01), the serum TNF-α, IL-1β and IL-6 were decreased significantly (t=8.17, 4.58, 6.54, P<0.01), the activity of SA-β-gal was decreased, and the expressions of Nrf2, p-Nrf2 were enhanced (t=6.42, 7.30, P<0.01), while the expression of p62 was reduced (t=4.62, P<0.01) in the treatment group.
ConclusionsRacanisodamine plays the protective effect of radiation-induced lung injury by alleviating inflammation associating with the activating of Nrf2-related pathway, which reversed radiation-induced cell senescence.
Key words:
Racanisodamine; Irradiation induced lung injury; Cell senescence; Inflammation; Fibrosis
Contributor Information
Guo Haochun
Department of Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, China
Chen Jiajia
Department of Radiotherapy, Lianshui People′s Hospital, Kangda College of Nanjing Medical University, Huai′an 223400
School of Clinical Medicine, Medical College of Yangzhou University, Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou 225009, China
Pu Juan
Department of Radiotherapy, Lianshui People′s Hospital, Kangda College of Nanjing Medical University, Huai′an 223400
School of Clinical Medicine, Medical College of Yangzhou University, Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou 225009, China
Ding Zhou
Department of Radiotherapy, Lianshui People′s Hospital, Kangda College of Nanjing Medical University, Huai′an 223400
Yu Hanxu
Department of Radiotherapy, Lianshui People′s Hospital, Kangda College of Nanjing Medical University, Huai′an 223400
Dong Lei
Department of Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, China
Zhang Haijun
Department of Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, China
Wang Wanpeng
Department of Radiotherapy, Lianshui People′s Hospital, Kangda College of Nanjing Medical University, Huai′an 223400
School of Clinical Medicine, Medical College of Yangzhou University, Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou 225009, China