下颌骨放射性骨坏死山羊动物模型的建立

目的建立下颌骨放射性骨坏死(osteoradionecrosis,ORN)山羊动物模型。方法6只成年山羊根据不同照射剂量随机分为3组(15、20、25Gy),照射前收集正常下颌骨影像学及病理学资料,资料收集完成后采用直线加速器按分组剂量对左侧下颌骨行单次照射。照射结束后45d在照射侧行拔牙术,拔牙后每周观察局部及全身情况,拔牙结束后3、6个月行影像学、病理学及骨代谢检查。结果在组织病理学检查上,3组均符合ORN,其严重程度与照射剂量正相关;其中20Gy和25Gy组有典型的临床症状出现;照射前后颌骨影像学检查无明显改变;骨代谢检查发现放疗侧颌骨代谢明显较对侧低。结论成功建立下颌骨ORN山羊动物模型。ORN组织细胞学及颌骨代谢变化先于影像学改变。     

自体骨髓间充质干细胞移植对小型猪下颌骨放射性骨坏死的预防作用

目的：观察和分析自体骨髓间充质干细胞（ bone marrow mesenchymal stem cells,BMMSCs）静脉输注移植是否对小型猪下颌骨放射性骨坏死（ osteoradionecrosis,ORN）有预防作用。方法照射前1个月分离培养扩增BMMSCs,在照射后不同时点实验组进行自体BMMSCs静脉输注移植,对照组静脉输注同体积不含细胞的细胞培养液。照射2个月后拔除左侧下颌第一恒磨牙,通过肉眼、CT以及组织病理学观察小型猪动物模型下颌骨是否发生ORN。结果照射2个月拔牙创伤后,两组动物均出现了组织水肿、皮肤溃烂、骨质破坏等。5个月后实验组动物皮肤愈合,随后CT显示破坏骨质修复,组织病理学显示为接近正常的骨组织,而对照组动物下颌骨仍呈典型ORN表现。结论自体BMMSCs移植对下颌骨ORN有一定的预防作用,其预防机制尚有待进一步研究。     

小型猪下颌骨放射性骨坏死动物模型的建立

目的 探讨利用小型猪建立下颌骨放射性骨坏死（ORN）动物模型的可行性。方法 应用三维适形放疗（3D-CRT）技术,采用电子直线加速器照射源对24只小型猪右侧下颌骨进行25 Gy和28 Gy一次性照射,于照射结束后2个月拔除双侧下颌第一磨牙,通过定期局部观察、X线、CT检查和组织病理学方法诊断下颌骨ORN的发生。结果 照射结束后3~4个月,拔牙后的小型猪先后全部发生了下颌骨ORN,28 Gy+拔牙组症状较重。结论 25 Gy单一剂量放射小型猪下颌骨+拔牙能建立有效的、可信的下颌骨ORN模型,可用于ORN病因学及治疗等方面的进一步研究。     

兔下颌骨放射性骨坏死模型的建立及评估

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。     

骨形态发生蛋白-2基因修饰骨髓间充质干细胞复合对氧化聚乙烯和聚丙烯共聚物移植促进兔下颌骨牵张成骨的实验研究

目的 探讨人骨形态发生蛋白-2（BMP-2）基因修饰骨髓间充质干细胞（BMSCs）复合可注射骨组织工程支架材料对氧化聚乙烯和聚丙烯共聚物（Pluronic F-127）移植对兔下颌骨牵张成骨新骨形成的促进作用。方法 将48只新西兰白兔随机分为4组,每组12只。建立下颌骨牵张成骨动物模型,固定期第2天A组于牵张间隙注射200 μL BMP-2基因修饰BMSCs与Pluronic F-127复合物;B组注射等量BMP-2基因修饰BMSCs液;C组注射等量BMSCs液;D组注射等量生理盐水。分别于固定2、6周时处死半数动物获取标本,通过X线片、组织切片及免疫组化观察骨质愈合改建情况。结果 通过X线片及免疫组化观察并经过统计软件分析,在固定2周和6周时,A组牵张区内骨密度和BMP-2蛋白的表达明显高于B、C、D组（P<0.01）,B组明显高于C组和D组（P<0.01）;C组和D组比较差异无统计学意义（P>0.05）。A、B组间隙内成骨质量好于C、D组,A组好于B组。结论 BMP-2基因修饰BMSCs复合可注射骨组织工程支架材料Pluronic F-127移植能有效促进兔下颌骨牵张成骨新骨形成。     

唑来膦酸剂量与颌骨坏死相关性的实验研究

目的 建立双膦酸盐相关性颌骨坏死的大鼠模型,分析双膦酸盐剂量与颌骨坏死发生之间的关系。方法 40只SD大鼠随机平均分为4组,腹腔注射剂量分别为33、66、132 μg/kg的唑来膦酸,对照组腹腔注射生理盐水,连续注射12周,每周3次,每周称重。第9周,拔除所有大鼠左侧下颌第一磨牙,第12周处死所有大鼠,取左侧下颌骨,进行影像学和组织病理学分析。采用SPSS19.0软件包对数据进行独立样本t检验。结果 实验组大鼠在拔牙后,体重显著低于对照组（P<0.05）,且X线片显示的拔牙创骨质密度也显著低于对照组（P<0.05）;实验组86.7%的大鼠拔牙创黏膜未完全愈合,而对照组所有大鼠拔牙创黏膜均完全愈合（P<0.05）。组织学检测发现,实验组70%的大鼠发生骨坏死,其中66、132 μg/kg骨坏死程度更为严重,而对照组组织学观察均未见骨坏死（P<0.05）。结论 BRONJ的发生和唑来膦酸的剂量有明显的相关性,低剂量唑来膦酸治疗只引起程度较轻的颌骨坏死,甚至不发生骨坏死,而高剂量唑来膦酸可引起严重骨坏死。     

下颌骨广泛的放射性骨坏死患者的治疗

下颌骨放射性骨坏死是任何时候对口腔相当量照射后的一种可能发生的后遗症。近年来,因照射方法,设备及牙齿处理的改进,放射性骨坏死的发病率已在下降。照射后下颌骨发生一系列变化,可分成三个类型,1.放射性骨萎缩。发生在所有经照射的下颌骨的患者中,X线片提示骨小梁结构粗糙,骨皮质轻度增厚和弥散的矿物质沉积,但骨块血运无明显改变。放射性骨萎缩患者可以无体症。2.无菌性放射性骨坏死,比放射性骨萎缩更进一步,但仍可以无体症。X线片指示骨小梁结构完全丧失。由     

引导组织再生膜促进兔下颌骨牵张成骨的实验研究

目的 探讨引导组织再生膜（GTRM）对兔下颌骨牵张成骨新骨形成的促进作用。方法 将20只新西兰大白兔随机分为2组,每组10只,建立兔下颌骨牵张成骨模型,A组单纯单侧下颌骨牵张成骨;B组将GTRM固定于牵张器内侧行单侧下颌骨牵张成骨。分别于固定期第2、6周时随机处死半数动物获取标本,通过X线、骨组织形态计量学比较2组牵张间隙内成骨效果。采用SPSS11.0软件包对数据进行两样本均数t检验。结果 通过X线及骨组织形态计量学检查并经过统计学分析发现,在固定期第2周和6周时,B组牵张区域内成骨质量显著好于A组（P<0.05）。结论 引导组织再生膜能有效促进兔下颌骨牵张成骨区域新骨的形成。     

31例放射性颌骨骨坏死(ORN)回顾性研究

目的:探讨放射性颌骨骨坏死(ORN)发病诱因及治疗手段。方法:对1995~2005年南京口腔医院颌面外科收治31例放射性颌骨骨坏死患者临床资料进行回顾性分析。结果:1)31例患者中患者原发头颈肿瘤来自鼻咽癌15例、腭癌5例、颊癌3例,余为咽、舌、口底、唾液腺癌等各1例。2)31例ORN患者接受放疗剂量由4 500~8 500 cGY。3)31例ORN患者下颌骨20例,上颌骨11例,两者之比近2∶1。4)高压氧 抗生素 创面死骨刮治术18例,抗生素 病灶搔刮术6例,抗生素 死骨切除术4例,单纯抗生素治疗3例。5)随诊痊愈17例,症状改善6例,死亡3例,失访5例。结论:1)放射性颌骨骨坏死(ORN)发病诱因同放疗剂量有关,7 000 cGY为临界点,统计结果存在显著性差异。2)下颌骨ORN与颌骨骨质结构、解剖位置以及体积有关。3)高压氧辅助抗生素控制感染,对于ORN仍是较为有效的治疗手段。     

hBMP-2基因修饰自体BMSCs移植促进兔下颌骨牵张成骨新骨形成的X线分析

目的:探讨hBMP-2基因修饰自体BMSCs移植对兔下颌骨牵张成骨新骨形成的促进作用。方法:取新西兰白兔36只随机分为3组,每组12只。建立牵张成骨动物模型,在固定期第2天,实验组于牵张间隙注射200μl的BMP-2基因修饰的自体BMSCs(2×105个细胞)悬液;对照组注射200μl的自体BMSCs(2×105个细胞)悬液;空白组注射200μl生理盐水。分别于固定2、6周摄X线片观察骨质愈合、改建情况。结果:通过X线观察并经过灰度值统计软件分析,在固定期2周及6周实验组牵张区骨密度明显高于对照组和空白组(P0.01)。结论:BMP-2基因修饰的自体BMSCs移植能有效促进兔下颌骨牵张成骨新骨形成。     

HDR brachytherapy irradiation of the jaw - as a new experimental model of radiogenic bone damage.

INTRODUCTION: Hitherto, no suitable experimental model exists to test new treatments for radiogenic bone damage, such as new step from knowledge about bone growth factors or angiogenesis factors. The goal of this investigation was to establish such a standardised experimental model. MATERIAL AND METHODS: Twenty-four rats were used in this study. In 12 rats a plastic tube was implanted along the right half of the mandible and treated with a single dose of 20 Gy at a high-dose-rate (HDR) using an afterloading machine, the remainder served as control (n=12). One hundred days after irradiation both sides of the mandible were examined using paraffin embedding and non-decalcified histology. RESULTS: All HDR irradiated rats developed localised alopecia within 2 weeks of radiotherapy. In the irradiated group, a clear growth reduction of the ipsilateral incisor was observed. Paraffin histology revealed minimal damage of the bone structure with slightly increased signs of regeneration. The bone apposition rate was significantly reduced on the irradiated right side, compared with the left side (p=0.028). The average diameter of the mandibular condyles on the irradiated right sides was significantly reduced when compared with the left sides (p=0.023). CONCLUSIONS: It is possible to induce radiogenic damage of the mandible by using HDR brachytherapy with a single dose of 20 Gy comparable to 45 x 2 Gy of conventional irradiation. This new model is easy and predictable and appears to be suitable for the testing of new treatment modalities. It is advantageous for the testing of bone growth and angiogenesis factors that the contralateral side exhibits completely normal bone apposition characteristics enabling a split-mouth design for future experiments.     

负载纳米羟磷灰石的结冷胶修复大鼠下颌骨缺损的效果评价

目的: 观察负载纳米羟磷灰石的结冷胶（GG/nHA）修复大鼠下颌骨缺损的效果。方法: 于16只SD大鼠下颌骨制备直径为5 mm的临界骨缺损,随机分为2组,实验组骨缺损区注入GG/nHA,对照组骨缺损区填充可吸收性明胶海绵。术后4周、8周处死大鼠,以Micro-CT定量分析骨组织愈合情况。苏木精-伊红（H-E）染色和马松（Masson）染色定性评估骨组织修复情况。采用GraphPad Prism 8.0软件包对数据进行统计学分析。结果: 制备的GG/nHA具有良好的可注射性,可经注射器推出至骨缺损区。术后4周和8周,实验组缺损区的骨生成量及骨体积分数（BV/TV）均显著高于对照组（P<0.05）。H-E染色和Masson染色均见实验组较对照组有更多新骨形成。结论: GG/nHA可以注射形式注入下颌骨缺损区,促进其愈合,有望成为微创修复口腔颌面部骨缺损的新型材料。     

Effects of pentoxifylline and tocopherol on an osteoradionecrosis animal model

PurposeOsteoradionecrosis (ORN) is known to be a refractory disease in the oral and maxillofacial field. The purpose of this study was to examine the effects of pentoxifylline (PTX) and tocopherol (TP) on an ORN animal model focused on bone healing.Materials and methodsA total of 48 Sprague–Dawley rats were used: 40 received a single irradiation dose of 35 Gy on the left mandible, and eight were used as the nonirradiated control group. The rats received PTX (T1, C1), TP (T2, C2), a combination of PTX and TP (T3, C3), or normal saline (T4, C4). Three weeks after irradiation, the mandibular posterior teeth were extracted. The rats were sacrificed 4 weeks after extraction.ResultsIn the T3 group, bone volume/tissue volume was 19.62 ± 16.03 (%), bone mineral density was as 0.31 ± 0.16 (g/cm³) in the micro-CT analysis, which were higher than that of other groups (p = 0.025, p = 0.012, respectively). In the histological analysis, bone regeneration was the most prominent in the T3 group. The ratio of empty lacunae was the highest in the T4 group, 68.77 ± 15.47 (%, p = 0.004). Immunohistochemistry showed that the expression of TNF-α was relatively lower in the T3 than in the T4 or T2 groups. The RT-qPCR showed the expression level of PECAM, VEGF-A, and osteocalcin was more than twofold as high as in the T3 group compared to the other groups.ConclusionThe combination of PTX and TP appears to promote angiogenesis and osteogenesis in a rat ORN model. Therefore, PTX and TP might be useful in the treatment and prevention of ORN.     

Osteodistraction of a previously irradiated mandible with or without adjunctive hyperbaric oxygenation: an experimental study in rabbits

The purpose of this study was to analyse the effects of irradiation and hyperbaric oxygenation (HBO) on mandibular osteodistraction (OD). Eighteen rabbits were divided into three groups: 1. Irradiation (R), 2. Irradiation+HBO (R-HO), and 3. Control group (C). Animals of groups R and R-HO received in the mandible irradiation 22.4 Gy in four 5.6 Gy fractions (equivalent to 50 Gy/25 fractions). In addition, group R-HO was given HBO at 2.5 ATA for 90 min per day 18 times preoperatively. Unilateral osteotomy was made 1 month after completion of radiotherapy. After a 1 week latency period bone distraction was started at rate of 1 mm per day, continued for 2 weeks, and left to consolidate for 4 weeks. Amount of new bone was measured histomorphometrically from midsagittal sections. Area of new bone was equal in all groups. Bone was more mature and bone spicules better organized in group C than in groups R and R-HO. Cartilaginous cells were found in distracted bone in all groups but larger chondroid islands were evident only in group R. It seems that despite delayed bone formation, OD can be performed after radiotherapy. HBO had a beneficial effect on bone quality of a previously irradiated mandible.     

下颌截骨术对兔颌骨非术区骨改建的影响

目的 :研究正颌手术对非手术区骨组织改建的影响,以更好地了解正颌手术加速颌骨改建的机制。方法 :12只新西兰大白兔随机分成4组,每组3只,9只行"双下颌骨磨牙区矢状截骨术"为手术组,3只为对照组。手术组9只按处死时间点分为术后1周组、3周组和8周组。每只动物单侧下颌骨用于Micro-CT扫描,对侧下颌骨用于组织学观察。结果:术后下颌骨整个骨组织发生吸收,在术后3周骨丧失最为显著,在术后8周骨形态恢复到近似对照组。下颌骨前牙区(非手术区)在术后1周至3周骨吸收较对照组活跃,表现为骨皮质内血管增生,出现破骨细胞和骨吸收陷窝,在术后3周达到高峰;在术后8周骨组织则与对照组无异。结论:正颌手术后,颌骨先是骨吸收活跃伴破骨细胞增多,骨改建加速,随后新骨生成,骨组织恢复。     

姜黄素对去势骨质疏松大鼠下颌骨和股骨EZH2基因表达的影响

目的 研究姜黄素对去势骨质疏松大鼠下颌骨和股骨EZH2（enhancer of zeste homolog 2,EZH2）表达的影响,探讨其对骨质疏松大鼠的保护作用及机制。方法 将30只6月龄SD雌性大鼠随机分为假手术组（SHAM组）、去势模型组（OVX组）和姜黄素治疗组(OVX+C组)。治疗组将姜黄素溶于羧甲基纤维素钠溶液后,按110 mg/kg·d灌胃给药;假手术组和去势模型组灌胃同等剂量羧甲基纤维素钠溶液,每天1次,连续12周后取材。检测大鼠血清钙、磷、碱性磷酸酶的指标变化,采用Micro-CT对左侧下颌骨和股骨的骨形态计量学参数进行测定。取右侧下颌骨和股骨,采用PT-PCR法检测骨组织EZH2mRNA的表达。采用SPSS22.0软件包对数据进行统计学分析。结果 OVX组骨组织中EZH2mRNA的表达显著高于SHAM组（P<0.05）。与OVX组相比,姜黄素可以改善骨质疏松大鼠的骨微结构,增加骨密度,降低骨质疏松大鼠血清碱性磷酸酶含量,使骨组织EZH2mRNA表达显著下调（P<0.05）。结论 姜黄素能够防治去势大鼠的骨量丢失和改善骨微结构,其机制可能与下调EZH2mRNA的表达水平有关。     

Evaluation of socket healing in irradiated rats after diode laser exposure (histological and morphometric studies)

ObjectiveThe purpose of this study is to evaluate the effect of low-level laser therapy (LLLT) in enhancing bone repair in irradiated sockets of albino rats.DesignThirty male Swiss Albino rats ranging from 120 to 150 g were used in this study. The animals were subjected 6 gray gamma radiations. Three days post irradiation, right and left mandibular first molars were extracted. The sockets of the left sides were irradiated by (GaAIAs) diode laser device immediately after extraction, while the sockets of the right side were not exposed to the laser and served as control. The rats were randomly assigned into three groups (10 rats each) according to the date of sacrifice, 3, 7 and 10 days into groups I, II and III, respectively. The two sides of each mandible were separated. Each group was further subdivided into subgroups A and B (10 specimens each), where A represents the right side of the mandible and B represents the left side. The specimens were stained with hematoxylin and eosin, and Masson's trichrome.ResultsLLLT accelerated bone healing, while, radiotherapy induced delay of bone healing along the three experimental groups. This acceleration was assessed histologically by the presence of mature collagen fibre bundles and early new bone formation in the lased groups. Histomorphometric analysis revealed an increase in the area percentage of bone trabeculae in the lased sockets compared to the control ones in group II. This increase was statistically significant (p = 0.0274). The increase in the area percentage of bone trabeculae between the lased and control sockets of group III was statistically insignificant (p = 0.1903).ConclusionsIn a rat model application of LLLT with a GaAIAs diode laser device can enhance bone healing and mineralisation in sockets subjected to gamma radiation.