Zhao Wendi,Tian Jian,Xuan Dandan,Zhang Xiuli,Li Chunmei,Zhou Jianwei.Prevention effect of low dose pre-irradiation on irradiation induced lung injury in mice and its possible mechanism[J].Chinese Journal of Radiological Medicine and Protection,2022,42(10):745-752
Prevention effect of low dose pre-irradiation on irradiation induced lung injury in mice and its possible mechanism
Received:December 27, 2021  
DOI:10.3760/cma.j.cn112271-20211227-00498
KeyWords:Ionizing radiation  Low dose  Prevention of radiation lung injury  Pulmonary fibrosis
FundProject:国家自然科学基金 (81673097)
Author NameAffiliationE-mail
Zhao Wendi Henan University People's Hospital, Henan Provincial People's Hospital Cancer Center, Zhengzhou 450003, China  
Tian Jian Henan University People's Hospital, Henan Provincial People's Hospital Cancer Center, Zhengzhou 450003, China  
Xuan Dandan Experimental Animal Center of Zhengzhou University, Zhengzhou 450003, China  
Zhang Xiuli Henan University People's Hospital, Henan Provincial People's Hospital Cancer Center, Zhengzhou 450003, China  
Li Chunmei Henan University People's Hospital, Henan Provincial People's Hospital Cancer Center, Zhengzhou 450003, China  
Zhou Jianwei Henan University People's Hospital, Henan Provincial People's Hospital Cancer Center, Zhengzhou 450003, China zhoujw666@163.com 
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Abstract::
      Objective To evaluate the prevention effect of low dose pre-irradiation on irradiation-induced lung injury and its possible mechanism.Methods Totally 320 6-week-old female C57BL/6j mice were divided into control (0 Gy), low-dose (0.5 Gy), high-dose (20 Gy) and low-dose pre-radiation(0.5 Gy+20 Gy)groups by the random number method, with 80 mice in each group. The mice in the low-dose and low-dose pre-irradiation groups were placed in the immobilization device under full consciousness and subjected to 0.5 Gy X-ray whole-body irradiation. 2 weeks later, the 0.5 Gy pre-irradiated mice were anesthetized and subjected to 20 Gy X-rays on chest, as the pre-radiation plus high dose radiation group. The mice in the control group were irradiated with mock irradiation (0 Gy). All mice were terminated at designed time points (24 h, 1 month, 3 months and 5 months) after completion of the irradiation schedule, with 20 mice/group at each time point. Then, lung tissues were taken from mice, and pathological changes were observed by hematoxylin-eosin (HE) staining and Masson's trichrome staining. RT-qPCR and Western blot were used to detect the expressions of mRNAs and proteins of pulmonary fibrosis-related factors.Results Pathological changes were observed in the lung tissues 1 month after a single high-dose 20 Gy irradiation, mainly including radiation pneumonitis and a small amount of collagen accumulation, which was more serious than low-dose pre-irradiation group, and these pathological changes became more severe when the time after irradiation increased. Meanwhile, the mRNA and protein levels of proSP-C and HOPX in the low-dose pre-irradiation group were higher than those in the high-dose group, except for proSP-C protein expression at 3 and 5 months post-irradiation. A more significant change was that the mRNA level of TGF-β1 in the high-dose group was 5.8-13.6 times higher than that in the other groups at 5 months after irradiation, as well as β-catenin mRNA (t=4.22, 5.11, P<0.05). At the same time, in the early period (24 h and 1 month) post-irradiation, the level of vimentin protein in the low-dose pre-irradiation group was significantly higher than that in the high-dose group (t=6.54, 4.28, P<0.05).Conclusions When the mice were pre-irradiated with 0.5 Gy X-rays, an adaptive protective response was induced in lung tissues, resulting in the tolerance to subsequent high dose irradiation.
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