兔下颌骨放射性骨坏死模型的建立及评估

中国口腔颌面外科杂志 ›› 2014, Vol. 12 ›› Issue (6): 481-486.

• 基础研究 • 下一篇

兔下颌骨放射性骨坏死模型的建立及评估

宗春琳¹, 郭宇轩¹, 窦庚², 张宇², 田磊^{1*, *}, 刘彦普^{1*, *}

1.第四军医大学口腔医学院口腔颌面外科;
2.第四军医大学学员旅,军事口腔医学国家重点实验室,陕西西安 710032

收稿日期:2014-06-24 出版日期:2014-11-10 发布日期:2015-01-01
通讯作者: 田磊,Tel：029-84776109,E-mail:tianleison@163.com;刘彦普,E-mail:Liuyanpu@fmmu.edu.cn。*共同通信作者
基金资助:
国家自然科学基金(81202150/H2201)

Establishment of a rabbit model for mandibular osteoradionecrosis

ZONG Chun-lin, GUO Yu-xuan, DOU Gen, ZHANG Yu, TIAN Lei, LIU Yan-pu

1.Department of Oral and Maxillofacial Surgery, School of Stomatology, 2. Student Brigade, Fourth Military Medical University;
State Key Laboratory of Military Stomatology. Xi’an 710032, Shaanxi Province, China

Received:2014-06-24 Online:2014-11-10 Published:2015-01-01
Supported by:
Supported by National Natural Science Foundation of China (81202150/H2201)

摘要/Abstract

摘要： 目的建立兔下颌骨放射性骨坏死动物模型,并通过大体观察、单光子发射计算机体层摄影（SPECT）、显微CT及组织病理学方法对该模型进行评估。方法将24只新西兰兔随机分为对照组和低、中、高3个剂量组,根据生物学等效公式,以低分割多次照射法,使用直线加速器对各组动物的左侧下颌区分别进行0、8.0、8.9和9.7 Gy照射,共5次。45 d后,拔除所有动物左侧下颌磨牙,3个月后,进行大体观察、SPECT、显微CT及组织病理学检查,采用SPSS17.0软件包对数据进行统计学处理。结果高剂量组动物死亡率较高。高、中剂量组出现照射区皮肤脱毛及照射侧拔牙创不愈合、下颌骨死骨形成并暴露;低剂量组脱毛不明显、拔牙创形成完整黏膜覆盖。组织学观察显示,高、中剂量组下颌骨有死骨形成及骨髓腔纤维化改变,低剂量组主要表现为髓腔炎症。SPECT显示,高、中剂量组代谢率较对照组显著降低。Micro-CT显示,高、中剂量组有死骨分离及骨皮质破坏,BV/TV、Tb.Th、Tb.N值下降,Tb.Sp值增加。结论以 8.9 Gy剂量对兔下颌区进行分割照射并在照射后拔牙,可成功建立下颌骨放射性骨坏死模型,在各项指标中均有明显放射性骨坏死表现,可重复性好,是研究下颌骨放射性骨坏死较为理想的动物模型。

关键词: 放射性颌骨骨坏死, 动物模型, 生物学等效剂量, 骨组织显微形态分析

Abstract: PURPOSE : The present study was performed to establish a standard animal model of mandibular osteoradionecrosis (ORN) in rabbit and to evaluate the irradiated mandibles based on clinical manifestation, single-photon emission computed tomography (SPECT), micro-CT, and histological observation. METHODS : According to the biological equivalent formula and hypofractionation radiation method, twenty-four rabbits were randomly divided into 4 groups: group 1 served as control, the left mandibles in group 2, 3 and 4 received iron irradiation at doses of 8.0, 8.9 and 9.7Gy every two days and 5 times respectively using linear accelerator. Forty-five days after irradiation, the left mandibular molars were extracted in all groups. Three months later, the mandibles in all groups were examined by clinical manifestation, SPECT, micro-CT, and histological observation to select the most suitable model. The data was analyzed with SPSS17.0 software package. RESULTS : Two rabbits died in group 4 because of malnutrition. Alopecia of the irradiated skin, sequestration and bone exposure in irradiated mandibles, and fibrosis in medulla were found in Group 3 and 4. In group 2, alopecia was less significant, and the mandibles had mainly showed medullary infection. Group 3 and 4 showed decreased BV/TV, Tb.Th, Tb.N and increased Tb.Sp compared to group 1 and 2. SPECT showed that bone metabolic rate in group 3 and 4 decreased significantly. CONCLUSION : We successfully established a reproducible rabbit model with mandibular osteoradionecrosis using iron radiation at dosage of 8.9 Gy with postradiation dental extractions. This model can serve as a platform for future studies on pathogenesis and treatment of ORN.

Key words: Osteoradionecrosis of jaws, Animal model, Biological equivalent dose, Bone histomorphometric analysis

中图分类号:

R782.4

宗春琳, 郭宇轩, 窦庚, 张宇, 田磊, 刘彦普. 兔下颌骨放射性骨坏死模型的建立及评估[J]. 中国口腔颌面外科杂志, 2014, 12(6): 481-486.

ZONG Chun-lin¹, GUO Yu-xuan¹, DOU Gen², ZHANG Yu², TIAN Lei¹, LIU Yan-pu¹. Establishment of a rabbit model for mandibular osteoradionecrosis[J]. China J Oral Maxillofac Surg, 2014, 12(6): 481-486.

参考文献

[1] Sciubba JJ, Goldenberg D. Oral complications of radiotherapy [J]. Lancet Oncol, 2006, 7(2): 175-183.
[2] Ko C, Citrin D. Radiotherapy for the management of locally advanced squamous cell carcinoma of the head and neck [J]. Oral Dis, 2009, 15(2): 121-132.
[3] Meyer OT, Dannenberg AM Jr. Radiation, infection, and macrophage function. II. Effect of whole body radiation on the number of pulmonary alveolar macrophages and their levels of hydrolytic enzymes[J]. J Reticuloendothel Soc,1970,7(1): 79-90.
[4] Marx RE. A new concept in the treatment of osteoradionecrosis [J]. J Oral Maxillofac Surg, 1983, 41(6): 351-357.
[5] Spiegelberg L, Djasim UM, Wolvius EB, et al. Hyperbaric oxygen therapy in the management of radiation-induced injury in the head and neck region: a review of the literature [J]. J Oral Maxillofac Surg, 2010, 68(8): 1732-1739.
[6] Rudolph R, Tripuraneni P, Koziol JA, et a1. Normal transcutaneous oxygen pressure in skin after radiation therapy for cancer [J]. Cancer, 1994, 74(11): 3063-3070.
[7] Shaw RJ, Dhanda J. Hyperbaric oxygen in the management of late radiation injury to the head and neck. Part I: treatment [J]. Br J Oral Maxillofac Surg, 2011, 49(1): 2-8.
[8] Annane D, Depondt J, Aubert P, et al. Hyperbaric oxygen therapy for radionecrosis of the jaw: a randomized, placebo-controlled, double blind trial from the ORN96 study group [J]. J Clin Oncol, 2004, 22(24):4893-4900.
[9] Madrid C, Abarca M, Bouferrache K. Osteoradionecrosis: an update [J]. Oral Oncol, 2010, 46(6): 471-474.
[10] Chrcanovic BR, Reher P, Sousa AA, et al. Osteoradionecrosis of the jaws-a current overview-part 1: physiopathology and risk and predisposing factors [J]. J Oral Maxillofac Surg, 2010, 14(1): 3-16.
[11] Delanian S, Lefaix JL. The radiation-induced fibroatrophic process: therapeutic perspective via the antioxidant pathway [J]. Radiother Oncol, 2004, 73(2): 119-131.
[12] 庄乾伟, 刘广龙, 何悦, 等. 转TGFβ1基因小鼠体内放疗敏感性初步评价 [J].中国口腔颌面外科杂志, 2013, 11(3): 183-191.
[13] Delanian S, Chatel C, Porcher R, et al. Complete restoration of refractory mandibular osteoradionecrosis by prolonged treatment with a pentoxifylline-tocopherol-clodronate combination (PENTOCLO): a phase II trial [J]. Int J Radiat Oncol Biol Phys, 2011, 80(3): 832-839.
[14] Cohen M, Nishimura I, Tamplen M, et al. Animal model of radiogenic bone damage to study mandibular osteoradionecrosis[J]. Am J Otolaryngol, 2011, 32(4): 291-300.
[15] Zhang WB, Zheng LW, Chua D, et al. Bone regeneration after radiotherapy in an animal model [J]. J Oral Maxillofac Surg, 2010, 68(11): 2802-2809.
[16] Wu G, Chen L, Qu T, et al. Ultrasonic treatment of canine ORNM [J].J Oral Maxillofac Surg, 2013, 71(1): 199-207.
[17] 贺捷, 何悦, 邱蔚六, 等. 下颌骨放射性骨坏死山羊动物模型的建立 [J]. 口腔医学, 2009, 29(9): 453-456.
[18] Xu J, Zheng Z, Fang D, et al. Early-stage pathogenic sequence of jaw osteoradionecrosis in vivo [J]. J Dent Res, 2012, 91(7): 702-708.
[19] Fenner M, Park J, Schulz N, et al. Validation of histologic changes induced by external irradiation in mandibular bone. An experimental animal model[J]. J Craniomaxillofac Surg,2010,38(1): 47-53.
[20] Ardran GM. Bone destruction not demonstrable by radiography [J]. Br J Radiol, 1951, 24(278): 107-109.
[21] Reuther T, Schuster T, Mende U, et al. Osteoradionecrosis of the jaws as a side effect of radiotherapy of head and neck tumour patients-a report of a thirty year retrospective review [J]. Int J Oral Maxillofac Surg, 2003, 32(3): 289-295.
[22] Kurihashi T, Iwata H, Nasu M, et al. Experimental study on wound healing of alveolar bone sockets in the rat maxilla after X-ray irradiation [J]. Odontology, 2002, 90(1): 35-42.

兔下颌骨放射性骨坏死模型的建立及评估

Establishment of a rabbit model for mandibular osteoradionecrosis

RichHTML

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 9

编辑推荐

Metrics

本文评价

[1]	张楚南, 赵旭, 乔士冲, 张晓梦, 顾迎新. 拔牙窝内植入不同深度骨水平种植体周围软硬组织改建的组织形态变化[J]. 中国口腔颌面外科杂志, 2021, 19(3): 193-196.
[2]	李璐, 邱宇, 黄立, 蒋志豪, 王日辉, 高炳菊, 李军, 廖云阳, 林李嵩. 骨质疏松SD大鼠药物相关性颌骨骨坏死模型的建立[J]. 中国口腔颌面外科杂志, 2019, 17(5): 403-411.
[3]	傅友, 许可, 李江, 孙树洋, 张志愿. 化学致癌剂4-NQO饮水法诱导小鼠口腔鳞癌模型的建立[J]. 中国口腔颌面外科杂志, 2019, 17(4): 300-303.
[4]	杜仲, 刘嘉靓, 郑家伟, 王延安. EGFL7在血管生成调控中的研究进展[J]. 中国口腔颌面外科杂志, 2019, 17(4): 377-381.
[5]	林海燕, 王仁飞, 于艳春, 邓力全, 张维丹, 林征宇. 比格犬上颌窦侧壁开窗术的路径探讨和效果分析[J]. 中国口腔颌面外科杂志, 2017, 15(6): 498-502.
[6]	彭昊，周国瑜，赵建鑫，沈玲悦，马川. 组织块法建立婴幼儿血管瘤动物模型的实验研究[J]. 中国口腔颌面外科杂志, 2015, 13(6): 486-490.
[7]	李凌志, 王丽珍, 何冬梅, 杨驰. 山羊颞下颌关节损伤模型的建立及组织学评价[J]. 中国口腔颌面外科杂志, 2014, 12(1): 13-19.
[8]	刘夏诚;杨雯君;张陈平;季彤;王丽珍;李江;黄谢山;白真玉. 兔舌癌哨位淋巴结微转移模型的建立 [J]. 中国口腔颌面外科杂志, 2013, 11(3): 192-198.
[9]	沈佩;张善勇;杨驰;黄栋. 发育期羊全颞下颌关节置换术后的下颌骨对称性评价 [J]. 中国口腔颌面外科杂志, 2013, 11(2): 107-111.