α2巨球蛋白对大鼠下颌骨放射性骨坏死的预防作用

doi:10.19438/j.cjoms.2018.02.006

中国口腔颌面外科杂志 ›› 2018, Vol. 16 ›› Issue (2): 126-131.doi: 10.19438/j.cjoms.2018.02.006

α2巨球蛋白对大鼠下颌骨放射性骨坏死的预防作用

李洁¹, 孔祥波², 陈雪英¹, 刘仰¹, 钟婉珍¹, 房思炼¹

1.中山大学附属第六医院口腔颌面外科,广东广州 510655;
2.中山大学孙逸仙纪念医院口腔科, 广东广州 510120;

收稿日期:2017-11-12 出版日期:2018-03-20 发布日期:2018-04-08
通讯作者: 房思炼,E-mail: fangsilian@126.com
作者简介:李洁（1990-）,女,硕士,E-mail:15862203588@163.com
基金资助:
广东省自然科学基金 (2015A030313064); 广东省科学技术基金 (2017A010105027)

Effect of alpha2-macroglobulin on osteoradionecrosis of mandible in rats

LI Jie¹, KONG Xiang-bo², CHEN Xue-ying¹, LIU Yang¹, ZHONG Wan-zhen¹, FANG Si-lian¹

1.Department of Oral and Maxillofacial Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University. Guangzhou 510655;
2.Department of Stomatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University. Guangzhou 510120, Guangdong Province, China;

Received:2017-11-12 Online:2018-03-20 Published:2018-04-08

摘要/Abstract

摘要： 目的: 观察和分析在X线照射前于大鼠下颌骨体局部注射α2巨球蛋白（alpha2-macroglobulin, α2M）是否对大鼠下颌骨放射性骨坏死（osteoradionecrosis,ORN）具有预防作用。 方法: 健康SD雄性大鼠18只,随机分为3组,每组6只。其中A组为空白对照组,B组为单纯X线照射组,C组为X线照射前左侧下颌骨局部注射α2M组。大鼠均经麻醉后使用3D打印装置固定,B、C组使用X线生物学辐照器对其左侧下颌骨进行精准照射,每天7 Gy,连续照射5 d;A组假照射;C组在第1次X线照射前30 min于大鼠左侧下颌骨体部骨膜下局部注射0.5 mL 2000 mg/L的α2M,A、B组在同样部位注射等量无菌生理盐水（normal saline,NS）。照射完成后第7天,拔除大鼠左侧下颌3颗磨牙。照射完成后第28天处死所有大鼠,从大体、影像学、病理学等方面系统评估各组大鼠的放射损伤。采用SPSS 13.0软件包对数据进行统计学分析。 结果: B组5只大鼠大体上体重明显减轻、照射区黏膜重度溃疡、受照侧颊部脱毛、咬合关系紊乱;影像学显示明显的骨质缺损;病理观察发现照射区皮质骨空白骨陷窝增多、死骨形成、纤维增生等骨坏死典型症状,证实发生下颌骨ORN,发生率为5/6;与B组相比,C组大鼠大体上仅表现为轻度体重下降及照射区脱毛,影像学上未见明显骨质缺损,病理观察仅见骨髓腔内轻微炎症,皮质骨无明显破坏,骨陷窝空虚率较B组显著降低（P<0.001）;C组大鼠下颌骨ORN发生率为零。 结论: X线照射前注射α2M对下颌骨ORN的发生具有较好的预防作用。

关键词: α2巨球蛋白, 大鼠, 放射性颌骨坏死

Abstract: PURPOSE: To investigate the effect of alpha2-macroglobulin (α2M) injected before irradiation on mandibular osteoradionecrosis (ORN) in rats. METHODS: Eighteen male Sprague-Dawley rats were divided randomly into 3 groups: group A (control group), group B (radiotherapy alone) and group C (α2M applied 30 minutes before radiotherapy). All the rats were fixed by 3D-printed fixator after anesthesia. Rats in group B and C underwent 7 Gy irradiation for 5 days to the left hemimandible; at the same time, rats in group A underwent shame irradiation. Rats in group C were injected 0.5 mL 2000 mg/L α2M in sterile saline solution along the left mandible, and rats in group A and group B were injected 0.5mL sterile normal saline. Seven days after irradiation, all left molar teeth were extracted. 21days later, the rats were sacrificed and the left mandible were examined by gross manifestation, microcomputed tomography, and histology. SPSS 13.0 software package was used for statistical analysis. RESULTS: Compared with group A, 5 rats in group B developed mandibular ORN. On gross observation, serious weight loss, alopecia of the irradiated skin, oral ulcer and occlusive disorder were seen in the rats of group B. Lack of new bone formation within the socket was seen on Micro-CT three-dimensional reconstruction. Haematoxylin-eosin and Masson's staining showed that inflammations, necrosis, and fibrosis in the medulla. The rate of mandibular ORN in group was 5/6. However, the rats in group C exhibited less weight loss, alopecia and no occlusive disorder, and slight inflammation in the bone marrow. The cortical bone was close to the normal bone on Micro-CT . The rate of osteocytic lacunae was decreased compared with group B (P<0.001). The rate of mandibular ORN in group C was zero. CONCLUSIONS: Application of α2M before radiotherapy could well prevent mandibular ORN and had a good application prospects.

Key words: Alpha2-macroglobulin, Rat, Osteoradionecrosis

中图分类号:

R782.2

李洁, 孔祥波, 陈雪英, 刘仰, 钟婉珍, 房思炼. α2巨球蛋白对大鼠下颌骨放射性骨坏死的预防作用[J]. 中国口腔颌面外科杂志, 2018, 16(2): 126-131.

LI Jie, KONG Xiang-bo, CHEN Xue-ying, LIU Yang, ZHONG Wan-zhen, FANG Si-lian. Effect of alpha2-macroglobulin on osteoradionecrosis of mandible in rats[J]. China J Oral Maxillofac Surg, 2018, 16(2): 126-131.

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α2巨球蛋白对大鼠下颌骨放射性骨坏死的预防作用

Effect of alpha2-macroglobulin on osteoradionecrosis of mandible in rats

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