低剂量辐射对小鼠肠道损伤的影响

摘要/Abstract

摘要： 采用3种不同低剂量(L组0.04 Gy/d、M组0.12 Gy/d、H组0.2 Gy/d)辐射对3组Balb/c小鼠进行连续5天的照射(分别累积照射0.2、0.6、1.0 Gy),设立对照组(NC),照射结束后测定小鼠体重、外周血象、脏器指数、小肠组织中丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性、免疫细胞因子(IL-1β、IL-2、IL-6、TNF-α)、DNA损伤、细胞凋亡等指标的变化。通过比较不同低剂量辐射下小鼠肠道损伤指标的变化,以探讨低剂量辐射小鼠肠道损伤最佳照射剂量,为低剂量辐射小鼠肠道损伤模型的建立提供科学依据。结果表明,连续照射5天后,各照射组相比于对照组,小鼠体重、脏器指数均有不同程度下降(脾脏指数L组p＜0.05、M、H组p＜0.01);小肠组织中MDA含量明显升高(L组p＜0.05、M、H组p＜0.01);SOD含量有不同程度下降;TNF-α、IL-2、IL-1β和IL-6作为代表性促炎因子呈剂量依赖性升高(IL-1β:M、H组p＜0.05,IL-2:M组p＜0.05、H组p＜0.01,TNF-α:M、H组p＜0.05);M、H组有明显DNA损伤及细胞凋亡。通过以上结果得出本次低剂量辐射小鼠肠道损伤模型的最佳照射剂量及方法为0.12 Gy/d连续照射5天累积0.6 Gy。

关键词: 低剂量辐射, 模型, 小鼠, 肠道

Abstract: Objective: To compare the changes of intestinal injury indexes in mice exposed to different low-dose radiation, so as to provide scientific basis for the establishment of intestinal injury model in mice exposed to low-dose radiation.Methods: Balb/c mice in three groups were irradiated with three different low dose rates (0.04 Gy/d, 0.12 Gy/d, and 0.2 Gy/d) for five consecutive days (cumulative exposure of 0.2, 0.6, and 1.0 Gy, respectively), and a control group (NC) was established. After the irradiation, the body weight, peripheral blood picture, organ index, malondialdehyde (MDA) content in small intestinal tissue, superoxide dismutase (SOD) activity, immune cytokine (IL-1β, IL-2, IL-6, TNF-α), DNA damage were determined, to explore the optimal dose of low dose radiation for intestinal injury in mice.Results: After five days of continuous irradiation, compared with the control group, the body weight and organ index of mice in each irradiation group were decreased to different extents (p< 0.05 in the spleen index L group, p< 0.01 in the M and H groups). MDA content in small intestinal tissue was significantly increased (p< 0.05 in Group L, and p< 0.01 in Group M and H); SOD content was decreased to different degrees. TNF-α, IL-2, IL-1β and IL-6, the typical proinflammatory factors, showed dose-dependent increases (IL-1β: M, group H p< 0.05, IL-2: M group p< 0.05, group H p< 0.01, TNF-α: M, group H p< 0.05). Group M and H had significant DNA damage and apoptosis.Conclusion: The optimal dose and method for low dose rate radiation induced intestinal injury in mice is 0.12 Gy/d continuous irradiation and 0.6 Gy accumulation for 5 days.

Key words: low dose radiation, model, mouse, intestinal

中图分类号:

R818

胡昌坤, 张雪梅, 马增春, 高月. 低剂量辐射对小鼠肠道损伤的影响[J]. 辐射防护, 2021, 41(4): 315-320.

HU Changkun, ZHANG Xuemei, MA Zenchun, GAO Yue. Effects of low dose radiation on intestinal injury in mice[J]. RADIATION PROTECTION, 2021, 41(4): 315-320.

参考文献

[1] Azzam E I. What does radiation biology tell us about potential health effects at low dose and low dose rates?[J]. J Radiol Prot, 2019, 39(4):S28-S39.
[2] Preston R J, Rühm W, Azzam E I, et al. Adverse outcome pathways, key events, and radiation risk assessment[J]. Int J Radiat Biol,2021, 97(6):804-814.
[3] Fouad Y A, Aanei C. Revisiting the hallmarks of cancer[J]. Am J Cancer Res, 2017, 7(5):1016-1036.
[4] Hatzi V I, Laskaratou D A, Mavragani I V, et al. Non-targeted radiation effects in vivo: A critical glance of the future in radiobiology[J]. Cancer Lett, 2015, 356:34-42.
[5] Kreuzer M, Auvinen A, Cardis E, et al. Low-dose ionising radiation and cardiovascular diseases—Strategies for molecular epidemiological studies in Europe[J]. Mutat Res Mutat Res, 2015, 764:90-100.
[6] Baselet B, Rombouts C, Benotmane AM, et al. Cardiovascular diseases related to ionizing radiation: The risk of low-dose exposure (Review)[J]. Int J Mol Med, 2016, 38(6):1623-1641.
[7] Salomaa S, Averbeck D, Ottolenghi A, et al. European low-dose radiation risk research strategy: future of research on biological effects at low doses[J]. Radiat Prot Dosimetry, 2015, 164(1-2):38-41.
[8] 杜彬,原杰,任石祺,等.不同剂量辐射对NOD/SCID小鼠肠损伤的影响[J].中国医学科学院学报,2018, 40(1):7-12.
DU B, YUAN J, REN Z Q, et al. Effect of different doses of radiation on intestinal injury in NOD/SCID mice[J]. Acta Academiae Medicinae Sinicae, 2018, 40(1):7-12.
[9] Preston R J, Jr Boice J D, Brill A B, et al. Uncertainties in estimating health risks associated with exposure to ionizing radiation[J]. J Radiol Prot, 2013, 33(3): 573-588.
[10] Bhanja P, Norris A, Gupta-Saraf P, et al. BCN057 induces intestinal stem cell repair and mitigates radiation-induced intestinal injury[J]. Stem Cell Res Ther, 2018, 9(1):26.
[11] Browne J E, Bruesewitz M R, Vrieze T J, et al. Technical note: Increased photon starvation artifacts at low helical pitch in ultra-low-dose CT[J]. Med Phys, 2019, 46(12):5538-5543.
[12] Lumniczky K, Impens N, Armengol G, et al. Low dose ionizing radiation effects on the immune system[J]. Environ Int, 2020, 106212.
[13] HUANG Y, GUO F, YAO D, et al. Surgery for chronic radiation enteritis: outcome and risk factors[J]. J Surg Res, 2016, 204(2):335-343.
[14] Candeias S M, Gaipl U S. The immune system in cancer prevention, development and therapy, Anticancer[J]. Agents Med Chem, 2016, (16):101-107.
[15] Flockerzi E, Schanz S, Rübe C E. Even low doses of radiation lead to DNA damage accumulation in lung tissue according to the genetically-defined DNA repair capacity[J]. Radiother Oncol, 2014, 111(2):212-218.
[16] Kreuzer M, Dufey F, Laurier D, et al. Mortality from internal and external radiation exposure in a cohort of male German uranium millers, 1946-2008[J]. Int Arch Occup Environ Health, 2015, 88(4):431-41.
[17] Cheda A, Nowosielska E M, Wrembel-Wargocka J, et al. Production of cytokines by peritoneal macrophages and splenocytes after exposures of mice to low doses of X-rays[J]. Radiat Environ Biophys, 2008, 47(2):275-83.
[18] Ina Y, Sakai K. Activation of immunological network by chronic low-dose-rate irradiation in wild-type mouse strains: analysis of immune cell populations and surface molecules[J]. Int J Radiat Biol, 2005, 81(10):721-729.
[19] Tada E, Yang C, Gobbel G T, et al. Long-term impairment of subependymal repopulation following damage by ionizing irradiation[J]. Experimental Neurology, 1999, 160(1):66-77.
[20] Hendry J H, Otsuka K. The role of gene mutations and gene products in intestinal tissue reactions from ionising radiation[J]. Mutat Res, 2016, 770(Pt B):328-339.
[21] Nagle P W, Hosper N A, Barazzuol L, et al. Lack of DNA damage response at low radiation doses in adult stem cells contributes to organ dysfunction[J]. Clin Cancer Res, 2018, 24(24):6583-6593.
[22] Moroni M, Maeda D, Whitnall M H, et al. Evaluation of the gamma-H2AX assay for radiation biodosimetry in a swine model[J]. Int J Mol Sci, 2013, 14(7):14119-14135.
[23] Gupta V, Somarajan B I, Walia G K, et al. Role of CYP1B1, p.E229K and p.R368H mutations among 120 families with sporadic juvenile onset open-angle glaucoma[J]. Graefes Arch Clin Exp Ophthalmol, 2018, 256(2):355-362.
[24] Kundrát P, Friedland W. Impact of intercellular induction of apoptosis on low-dose radiation carcinogenesis[J]. Radiat Prot Dosimetry, 2015, 166(1-4):170-173.
[25] Babini G, Morini J, Baiocco G, et al. In vitro γ-ray-induced inflammatory response is dominated by culturing conditions rather than radiation exposures[J]. Sci Rep, 2015, 5:9343.
[26] Babini G, Ugolini M, Morini J, et al. Investigation of radiation-induced multilayered signalling response of the inflammatory pathway[J]. Radiat Prot Dosimetry, 2015, 166(1-4):157-160.
[27] Suman S, Kumar S, Moon B H, et al. Low and high dose rate heavy ion radiation-induced intestinal and colonic tumorigenesis in APC1638N/+ mice[J]. Life Sci Space Res (Amst), 2017, 13:45-50.