Guo Haochun,Chen Jiajia,Pu Juan,Ding Zhou,Yu Hanxu,Dong Lei,Zhang Haijun,Wang Wanpeng.Mechanism of racanisodamine on alleviating radiation-induced lung injury in mice[J].Chinese Journal of Radiological Medicine and Protection,2023,43(6):418-424
Mechanism of racanisodamine on alleviating radiation-induced lung injury in mice
Received:February 10, 2023  
DOI:10.3760/cma.j.cn112271-20230210-00032
KeyWords:Racanisodamine  Irradiation induced lung injury  Cell senescence  Inflammation  Fibrosis
FundProject:江苏省卫生健康委指导性课题(Z2020022);淮安市自然科学研究计划项目(HAB202251)
Author NameAffiliationE-mail
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 
wangwanpeng123@163.com 
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Abstract::
      Objective To investigate the protective effect of racanisodamine on lung injury in mice exposed to irradiation.Methods C57BL/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.Results Compared 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.Conclusions Racanisodamine 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.
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