| 赵文迪,田健,轩丹丹,张秀丽,李春梅,周建炜.低剂量预照射对小鼠放射性肺损伤的预防作用及其可能的机制[J].中华放射医学与防护杂志,2022,42(10):745-752 |
| 低剂量预照射对小鼠放射性肺损伤的预防作用及其可能的机制 |
| Prevention effect of low dose pre-irradiation on irradiation induced lung injury in mice and its possible mechanism |
| 投稿时间：2021-12-27 |
| DOI：10.3760/cma.j.cn112271-20211227-00498 |
| 中文关键词: 电离辐射 低剂量 放射性肺损伤预防 肺纤维化 |
| 英文关键词:Ionizing radiation Low dose Prevention of radiation lung injury Pulmonary fibrosis |
| 基金项目:国家自然科学基金 (81673097) |
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| 摘要点击次数: 1943 |
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| 中文摘要: |
| 目的 评估低剂量辐射预照射对放射性肺损伤的预防作用及其可能机制。方法 320只6周龄雌性C57BL/6j小鼠用随机数表法将其分为对照组(0 Gy)、低剂量组(0.5 Gy)、高剂量组(20 Gy)和低剂量预照射组(0.5 Gy+20 Gy),每组80只。将低剂量组和低剂量预照射组的小鼠于充分清醒的状态下放入固定装置中进行0.5 Gy低剂量X射线全身照射。2周后将高剂量组和低剂量预照射组的小鼠进行麻醉,行20 Gy的高剂量X射线胸部照射。而对照组小鼠行模拟照射(0 Gy)。所有小鼠在完成照射计划后按照设计的时间点(24 h、1个月、3个月和5个月)进行处理,每个时间点处理小鼠20只/组。取小鼠肺组织标本,采用苏木精-伊红染色法(HE染色)和Masson三色染色法观察病理变化;RT-qPCR和Western blot检测肺纤维化相关因子mRNA和蛋白的表达。结果 单次高剂量20 Gy照射后1个月的肺组织发生病理改变,主要表现为放射性肺炎和少量胶原蛋白堆积,随着照射后时间的递增,病理改变越为严重;而低剂量预照射组在各个时间点的肺组织病理学改变均较高剂量组的轻。同时,除照射后3个月和5个月组的proSP-C蛋白外,低剂量预照射组的proSP-C和HOPX的mRNA和蛋白水不同程度地高于高剂量组。更为显著变化的是,高剂量组TGF-β1的mRNA 水平在照射后5个月时是其他组的5.8~13.6倍。 在照射后5个月,高剂量组β-catenin的mRNA和蛋白水平均远高于低剂量预照射组 (t=4.22、5.11,P<0.05)。同时,在照射后24 h和1个月的低剂量预照射组vimentin蛋白水平显著高于高剂量组(t=6.54、4.28,P<0.05)。结论 生物组织接受0.5 Gy低剂量电离辐射预照射可诱导正常组织产生适应性保护反应,进而对后续的治疗剂量的辐射产生耐受作用。 |
| 英文摘要: |
| 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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