不同辐照仪对大鼠下颌骨放射性颌骨坏死模型建立的影响

doi:10.7518/hxkq.2021.05.005

摘要/Abstract

摘要： 目的

比较不同辐照仪对大鼠放射性颌骨坏死（ORNJ）模型建立的影响，探索理想建模方法。

方法

将33只成年SD大鼠随机分为CN组（空白对照，3只）、A组（直线加速器照射，15只）、B组（小动物辐照仪照射，15只）。A、B组再次随机分为3组：A₃₅/B₃₅、A₄₀/B₄₀、A₄₅/B₄₅，各组左侧下颌骨分别接受每天7、8、9 Gy照射，连续5 d。照射结束后1周，所有大鼠行左侧下颌骨照射区拔牙创伤，3周后处死，获取下颌骨标本，进行大体观察、micro-CT扫描和组织病理学观察，评估建模成功率。

结果

拔牙后3周，A₃₅、A₄₀组拔牙创愈合，A₄₅、B组拔牙创未愈合、明显骨外露。苏木精-伊红染色见A₃₅组无死骨形成，A₄₀、A₄₅和B组明显死骨形成。A组建模成功率为40%，B组建模成功率为93.3%。

结论

小动物生物辐照仪是理想的大鼠ORNJ建模照射方式。

关键词: 直线加速器, 小动物生物辐照仪, 放射性颌骨坏死, 模型

Abstract: Objective

To compare the effects of different irradiators on the establishment of osteoradionecrosis of jaw model (ORNJ) to explore an ideal modeling method.

Methods

A total of 33 adult SD rats were included and randomly divided into three groups according to the radiation equipment, namely, the blank control (CN, 3 rats), group A (linear accelerator irradiation, 15 rats), and group B (small-animal irradiator irradiation, 15 rats). Groups A and B were irradiated with daily fractions of 7, 8, and 9 Gy for 5 days and further divided into three subgroups as follows: group A₃₅/B₃₅, 35 Gy; group A₄₀/B₄₀, 40 Gy; and group A₄₅/B₄₅, 45 Gy. The left mandibular molars of the rats were extracted 1 week after irradiation. The rats were sacrificed 3 weeks after tooth extraction, and the mandible specimens were obtained for gross observation, micro-CT scanning, and histological detection to evaluate the success rate of modeling.

Results

At 3 weeks after dental extractions, complete gingival healing was found in the regions of dental extractions in groups A₃₅ and A₄₀. However, failed gingival healing and bone exposure were found in groups A₄₅ and B. Hematoxylin and eosin staining showed necrotic bone of the irradiated mandible in groups A₄₀, A₄₅,_{and B, with success modeling rates of 40% in group A and 93.3% in group B.}

Conclusion

Small-animal irradiator irradiation is an ideal device for establishing ORNJ model.

Key words: linear accelerator, small-animal irradiator, osteoradionecrosis of jaw, model

中图分类号:

R 782

陈滑维, 张圣福, 何海涛. 不同辐照仪对大鼠下颌骨放射性颌骨坏死模型建立的影响[J]. 华西口腔医学杂志, 2021, 39(5): 524-530.

Chen Huawei, Zhang Shengfu, He Haitao.. Effects of different irradiators on the establishment of osteoradionecrosis model of rat mandible[J]. West China Journal of Stomatology, 2021, 39(5): 524-530.

图/表 7

图 1

表 1

图 2

图 3

图 4

图 5

图 6

参考文献 21

1	Hansen T, Wagner W, Kirkpatrick CJ, et al. Infected osteoradionecrosis of the mandible: follow-up study suggests deterioration in outcome for patients with Actinomyces-positive bone biopsies[J]. Int J Oral Maxillofac Surg, 2006, 35(11): 1001-1004.
2	Raggio BS, Winters R. Modern management of osteoradionecrosis[J]. Curr Opin Otolaryngol Head Neck Surg, 2018, 26(4): 254-259
3	He Y, Ma C, Hou J, et al. Chinese expert group consensus on diagnosis and clinical management of osteoradionecrosis of the mandible[J]. Int J Oral Maxillofac Surg, 2020, 49(3): 411-419.
4	Dhanda J, Pasquier D, Newman L, et al. Current conce-pts in osteoradionecrosis after head and neck radiotherapy[J]. Clin Oncol (R Coll Radiol), 2016, 28(7): 459-466.
5	Zhang ZR, Xiao WW, Jia JQ, et al. The effect of combined application of pentoxifylline and vitamin E for the treatment of osteoradionecrosis of the jaws: a Meta-ana-lysis[J]. Oral Surg Oral Med Oral Pathol Oral Radiol, 2020, 129(3): 207-214.
6	Marx RE. Osteoradionecrosis: a new concept of its patho-physiology[J]. J Oral Maxillofac Surg, 1983, 41(5): 283-288.
7	Delanian S, Lefaix JL. The radiation-induced fibroatro-phic process: therapeutic perspective via the antioxidant pathway[J]. Radiother Oncol, 2004, 73(2): 119-131.
8	Nadella KR, Kodali RM, Guttikonda LK, et al. Osteoradionecrosis of the jaws: clinico-therapeutic management: a literature review and update[J]. J Maxillofac Oral Surg, 2015, 14(4): 891-901.
9	Janus JR, Jackson RS, Lees KA, et al. Human adipose-derived mesenchymal stem cells for osseous rehabilitation of induced osteoradionecrosis: a rodent model[J]. Otolaryngol Head Neck Surg, 2017, 156(4): 616-621.
10	Yamasaki MC, Roque-Torres GD, Peroni LV, et al. A modified protocol of mandibular osteoradionecrosis induction in rats with external beam radiation therapy[J]. Clin Oral Investig, 2020, 24(4): 1561-1567.
11	Li J, Kong XB, Chen XY, et al. Protective role of α2-ma-croglobulin against jaw osteoradionecrosis in a preclinical rat model[J]. J Oral Pathol Med, 2019, 48(2): 166-173.
12	Chronopoulos A, Zarra T, Ehrenfeld M, et al. Osteoradionecrosis of the jaws: definition, epidemiology, staging and clinical and radiological findings. A concise review[J]. Int Dent J, 2018, 68(1): 22-30.
13	Zhang WC, Zhang XD, Yang P, et al. Intensity-modulated proton therapy and osteoradionecrosis in oropharyngeal cancer[J]. Radiother Oncol, 2017, 123(3): 401-405.
14	Jackson RS, Voss SG, Wilson ZC, et al. An athymic rat model for mandibular osteoradionecrosis allowing for direct translation of regenerative treatments[J]. Otolaryngol Head Neck Surg, 2015, 153(4): 526-531.
15	Li J, Yin P, Chen XY, et al. Effect of α2‑macroglobulin in the early stage of jaw osteoradionecrosis[J]. Int J Oncol, 2020, 57(1): 213-222.
16	Park HS, Lee J, Kim JW, et al. Preventive effects of tonsil-derived mesenchymal stem cells on osteoradionecrosis in a rat model[J]. Head Neck, 2018, 40(3): 526-535.
17	Rivero JA, Shamji O, Kolokythas A. Osteoradionecrosis: a review of pathophysiology, prevention and pharmacologic management using pentoxifylline, α-tocopherol, and clodronate[J]. Oral Surg Oral Med Oral Pathol Oral Radiol, 2017, 124(5): 464-471.
18	李洁, 孔祥波, 刘仰, 等. 短期内建立大鼠放射性颌骨坏死模型的改良及其临床病理和影像学动态评价[J]. 中国耳鼻咽喉头颈外科, 2018, 25(3): 115-119.
	Li J, Kong XB, Liu Y, et al. Establishment of an modified animal model of radionecrosis of the jaws in the short term and dynamic observation of clinical, pathological and imaging features[J]. Chin Arch Otolaryngol Head Neck Surg, 2018, 25(3): 115-119.
19	Tchanque-Fossuo CN, Monson LA, Farberg AS, et al. Dose-response effect of human equivalent radiation in the murine mandible: part Ⅰ. A histomorphometric asses-sment[J]. Plast Reconstr Surg, 2011, 128(1): 114-121.
20	Lyons A, Osher J, Warner E, et al. Osteoradionecrosis: a review of current concepts in defining the extent of the disease and a new classification proposal[J]. Br J Oral Maxillofac Surg, 2014, 52(5): 392-395.
21	He Y, Liu Z, Tian Z, et al. Retrospective analysis of osteoradionecrosis of the mandible: proposing a novel clinical classification and staging system[J]. Int J Oral Maxillofac Surg, 2015, 44(12): 1547-1557.

时间	CN组	A组			B组
时间	CN组	35 Gy	40 Gy	45 Gy	35 Gy	40 Gy	45 Gy
照射前	0.312 2±0.007 2	0.310 0±0.014 1	0.316 7±0.012 5	0.310 0±0.003 9	0.309 8±0.018 7	0.313 8±0.010 0	0.313 4±0.008 7
照射结束时	0.330 6±0.014 6	0.274 0±0.0114	0.273 0±0.013 1	0.274 8±0.021 3	0.318 0±0.022 5	0.322 7±0.009 7	0.314 5±0.010 7
照射后1周	0.370 8±0.012 0	0.237 0±0.015 1	0.226 7±0.037 7	0.201 0±0.017 2	0.342 7±0.032 9	0.324 3±0.056 2	0.288 3±0.016 4
拔牙后3周	0.442 6±0.033 2	0.346 7±0.006 2	0.314 0±0.006 5	0.265 0±0.022 5	0.443 3±0.059 5	0.437 3±0.046 3	0.406 3±0.041 1

[1]	严鑫淼, 孙桃兰, 卢雨航, 谭馨, 王卓, 李淼晶. 基于机器学习的四川省12岁儿童龋齿预测模型[J]. 华西口腔医学杂志, 2023, 41(6): 686-693.
[2]	卢妍竹, 张婧琦, 赖文莉. 大鼠三叉神经痛模型中小胶质细胞激活情况及经时变化[J]. 华西口腔医学杂志, 2022, 40(6): 638-644.
[3]	李博, 许益蒙, 史睿颖, 胡忆戎, 刘思颖, 顾泽旭. 无托槽隐形矫治进展评估功能的准确性研究[J]. 华西口腔医学杂志, 2022, 40(6): 698-703.
[4]	岳蔷薇, 徐乐, 张东升. 基于YTHDC2、IGF2BP2和HNRNPC的头颈部鳞状细胞癌N6-甲基腺苷风险模型构建及临床应用评估[J]. 华西口腔医学杂志, 2022, 40(6): 704-709.
[5]	秦硕, 李春梅, 李冉, 胡爽, 李光辉, 孙明磊. 术前外周血炎症指标对舌鳞状细胞癌预后预测价值的分析[J]. 华西口腔医学杂志, 2022, 40(3): 335-340.
[6]	刘超峰, 许艳华, 易春艳, 刘彦. Andrews六要素用于正畸病例数字化资料的临床回顾性研究[J]. 华西口腔医学杂志, 2022, 40(2): 183-188.
[7]	林超, 张心怡, 田洪雨, 栾可峰, 孙昊, 范欣. 潍坊市7~8岁儿童口腔卫生服务利用影响因素研究[J]. 华西口腔医学杂志, 2022, 40(2): 197-203.
[8]	卢嘉仪, 赵君仪, 高静, 于海洋. 1 312件单冠预备体数字化模型的关键预备质量指标的分析研究[J]. 华西口腔医学杂志, 2022, 40(1): 52-60.
[9]	张志愿, 孙树洋. 转化医学视角下头颈癌人源性肿瘤异种移植瘤模型队列的研究愿景[J]. 华西口腔医学杂志, 2021, 39(6): 617-623.
[10]	张建国, 刘隽, 岑蓉, 胡凤玲. 连续波充填技术对牙周组织温度影响的三维有限元分析[J]. 华西口腔医学杂志, 2021, 39(4): 447-452.
[11]	张颖, 贾松菠, 李帆, 李姗姗, 张利娟, 谭凯璇, 卢洁, 杨芳. 低龄儿童龋病相关的唾液生化指标研究[J]. 华西口腔医学杂志, 2021, 39(3): 300-305.
[12]	赵格, 黎昌学, 郭超, 朱慧. 基于生物信息学分析的口腔鳞状细胞癌微小RNA预后模型[J]. 华西口腔医学杂志, 2020, 38(6): 622-627.
[13]	付汉斌, 罗琳. HOX反义基因间RNA在唾液腺腺样囊性癌组织中的表达及对预后的影响[J]. 华西口腔医学杂志, 2020, 38(5): 509-512.
[14]	程俊鑫, 白贺天, 常治楠, 李敬, 陈谦明. 口腔黏膜癌前病变和口腔癌动物模型的研究进展[J]. 华西口腔医学杂志, 2020, 38(2): 198-204.
[15]	杨博,符梦凡,唐瞻贵. 槟榔碱及机械刺激构建大鼠口腔黏膜下纤维化模型[J]. 华西口腔医学杂志, 2019, 37(3): 260-264.