咬肌神经切除和化学去神经对大鼠下颌骨生长发育影响的实验研究
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摘要
研究背景
随着近年来颅颌面外科的发展,面部轮廓整形美容逐渐成为整形外科关注的热点之一。下颌角和咬肌肥大是东亚各民族常见的面部轮廓缺陷。随着微创外科和非手术整形美容技术的发展,下颌角和咬肌肥大的治疗也有向微侵袭技术发展的趋势,如咬肌去神经、射频消融等微创手术和A型肉毒毒素咬肌注射等非手术整形技术等。2004年Hwang首次报道了4例选择性咬肌神经切除术。1994年Moore应用A型肉毒毒素治疗咬肌肥大,2000年国内学者用国产肉毒毒素治疗咬肌肥大,收到了良好的治疗效果。
下颌骨的生长发育是一个连续的过程,通过调节骨沉积和骨吸收之间的平衡,下颌骨完成生长和重塑,青春期下颌骨的生长发育尤为重要。随着整形美容外科的发展,整形美容手术的安全性不断提高,并发症减少,逐渐在改变人们对整形美容的认知,越来越多的人寻求整形美容手术的帮助；求美者数量急剧增加的同时,求美者的年龄也呈现年轻化趋势,越来越多的青少年接受整形美容治疗。而微创技术和非手术整形美容技术由于非侵袭性、创伤小、恢复快、简单有效等优点更易使求美者呈现年轻化趋势。下颌骨生长发育的连续性和求美者的年轻化趋势,使面部轮廓整形美容面临新的问题：青春期前接受咬肌神经切除术或A型肉毒毒素咬肌注射,对青春期下颌骨的生长发育有无影响?对成年后下颌骨的形态、组织学、超微结构、骨密度、生物力学等方面产生怎样的影响?这些问题亟待在临床广泛应用之前进行深入研究和探讨。
目的
本研究拟对咬肌神经切除和化学去神经(咬肌注射A型肉毒毒素)后下颌骨的形态学、组织学、超微结构、骨密度、生物力学等方面的改变进行初步研究。实验分别切除幼龄大鼠一侧咬肌神经和在幼龄大鼠一侧咬肌肌内注射A型肉毒毒素,构建咬肌去神经和咬肌化学去神经的动物模型。待大鼠成年后,利用CT三维重建技术测量其下颌骨的长度、高度、下颌间距,对下颌骨进行组织学、超微结构的观察,测量下颌骨的骨密度,并利用有限元方法对下颌骨进行初步的生物力学分析,以期为咬肌神经切除和化学去神经后下颌骨的生物学研究提供参考。
方法
1.实验动物和分组：出生后21日龄断乳的雄性Wistar大鼠30只随机分成4组：手术组9只,切除右侧咬肌神经；假手术组9只,显露但不切除右侧咬肌神经；肉毒毒素组6只,右侧咬肌肌内注射A型肉毒毒素,左侧咬肌肌内注射生理盐水；对照组6只,仅将大鼠麻醉。
2.手术组、假手术组动物模型的建立：大鼠28日龄时进行实验,显微外科操作暴露咬肌神经主干及其分支,切断2-3 mm咬肌神经主干及部分分支。假手术组仅暴露右侧咬肌神经,不切除。
3.肉毒毒素组动物模型的建立：大鼠28日龄时进行实验,向右侧咬肌浅、深层各注射A型肉毒毒素0.05ml,共0.1ml即2U,向左侧咬肌浅、深层各注射生理盐水0.05ml,共0.1ml。
4.CT扫描和下颌骨测量：各组大鼠75日龄时,予10%水合氯醛腹腔注射麻醉后,行头颅CT平扫,用PHILIPS Brilliance TM CT工作站软件三维重建双侧下颌骨,确定测量标志点：Cor：冠突最上点；Con：髁突后上点；Go：下颌角后上点；GoT：下颌角最下点；Ma：下颌骨牙槽嵴上缘最凹点；Iia：下颌中切牙牙槽骨前下点；Me：下颌联合最下点。测量相关标志点间的线距：①下颌骨长度：下颌骨长度Ⅰ(Cor-Iia)、下颌骨长度Ⅱ(Con-Iia)、下颌骨长度Ⅲ(Go-Iia)。②下颌骨高度：下颌骨高度Ⅰ(Ma-Me)、下颌骨高度Ⅱ(Cor-GoT)、下颌骨高度Ⅲ(Con-GoT)。③下颌间距(GoT1-GoT2)
5.称量咬肌质量：CT扫描、测量完成后,各组大鼠予过量水合氯醛麻醉致死,完整切取双侧咬肌,迅速用电子天平称取新鲜咬肌质量并记录。
6.组织学、超微结构、免疫组化染色观察：取各组大鼠完整下颌骨,用4%多聚甲醛溶液固定1-2小时后,予10%EDTA溶液脱钙3周,取下颌角区、下颌体部、髁突各5mm×5mm大小骨组织,HE染色后行组织学观察；各组下颌骨标本用0.1mmol/1的PBS缓冲液冲洗后,用2.5%戊二醛溶液4℃固定24小时,经脱水、临界点干燥、真空喷金镀膜后行超微结构观察；组织白片行IL-6、TNF-α免疫组化染色,观察IL-6、TNF-α在下颌骨组织中的表达。
7.骨密度测量：取各组双侧完整下颌骨,利用en CORE 2006 V10.50.086分析软件中的小动物软件,在双能X线骨密度仪下测量感兴趣区的骨密度,兴趣区界定为咬肌附着区域。
8.有限元分析：将CT扫描获得的DICOM数据文件导入Mimics软件,行图像分割、阈值分割、区域增长、Calculate 3D后生成初步的下颌骨三维模型。用Mimics中FEA模块的Remesh功能,对三维模型进行表面优化和修洁处理。利用MSC.Patran软件,创建实体单元,生成四面体实体网格模型。根据Mimics中CT断层图像的大鼠下颌骨各部位的灰度值,计算求得最大弹性模量1200MPa,最小弹性模量1MPa,泊松比设为0.3。采用MSC.Marc软件对下颌支和下颌角行有限元分析,模拟三点弯曲试验。下颌支施加载荷点为下颌支的中心点,施加200N的力；下颌角施加载荷点为下颌角后上点,施加1ON的力。设置载荷在1秒内分10步完成,求解下颌支、下颌角的最大应力、最大应变、最大外力、最大位移。
9.统计学分析：采用SPSS 13.0统计软件分析,实验数据的计量资料以均数±标准差(x±s)表示,组内左、右侧的比较用配对t检验,组间比较用独立样本t检验和单因素方差分析,多重比较用LSD-t检验,以P<0.05为差异有统计学意义。
结果
1.一般情况：手术组、假手术组18只大鼠全部成活,术后无死亡。肉毒毒素组有2只大鼠发生偏颌。大体观察：手术组右侧咬肌萎缩,肉毒毒素组右侧咬肌明显萎缩,假手术组、对照组双侧咬肌饱满。
2.体重和咬肌质量：手术组、假手术组术前和术后体重差异无统计学意义。除注射后第1周,肉毒毒素组体重小于对照组外,注射前、后肉毒毒素组和对照组体重差异无统计学意义。手术组右侧咬肌质量小于左侧(P=0.000)；右侧咬肌质量小于假手术组和对照组(均P<0.05)。肉毒毒素组右侧咬肌质量小于左侧(P=0.001)；左、右两侧咬肌质量均小于对照组(P=0.016、P=0.000)。
3.下颌骨测量结果：
3.1手术组、假手术组
(1)组内左、右两侧比较：手术组右侧下颌骨高度Ⅱ(12.0±0.3mm)、下颌骨高度Ⅲ(9.4±0.4mm)小于左侧(分别为12.6±0.4mm.10.5±0.3mm)(P分别为P=0.001、P=0.000),假手术组右侧下颌骨高度Ⅲ(9.6±0.4mm)小于左侧(10.6±0.4mm)(P=0.000)。
(2)各组右侧线距的比较：下颌骨长度和下颌骨高度Ⅰ,各组之间差异无统计学意义。手术组下颌骨高度Ⅱ(12.0±0.3mm)小于对照组(P=0.017)。手术组、假手术组下颌骨高度Ⅲ(分别为9.4±0.4mm、9.6±0.4mm)小于对照组(均为P=0.000)。
(3)下颌间距比较：手术组小于对照组(P=0.018)。
3.2肉毒毒素组
(1)组内左、右两侧比较：肉毒毒素组右侧下颌骨长度Ⅲ(19.2±1.4mm)小于左侧(20.4±1.4mm),右侧下颌骨高度Ⅱ(10.8±0.8mm)小于左侧(12.0±0.9mm)(P分别为P=0.033、P=0.001)。
(2)右侧线距的比较：下颌骨长度和下颌骨高度Ⅰ肉毒毒素组与对照组比较,差异无统计学意义；肉毒毒素组下颌骨高度Ⅱ(10.8±0.8mm)、下颌骨高度Ⅲ(9.5±0.6mm)均小于对照组(P分别为P=0.007、P=0.005)。
(3)下颌间距：肉毒毒素组(11.6±0.6mm)小于对照组(12.4±0.6 mm),但差异无统计学意义。
4.组织学观察：手术组、假手术组、对照组下颌骨皮质骨致密,骨小梁丰富,骨陷窝大小、分布均一；肉毒毒素组下颌骨皮质骨致密,骨小梁欠丰富,骨陷窝大小、分布不均,部分骨细胞核细长。肉毒毒素组髁突软骨分层不明显,细胞染色较淡；对照组髁突软骨染色清晰,分层明显。
5.超微结构观察：对照组皮质骨致密,髁突部骨小梁数目较多,厚度较均匀,骨小梁的间隙较小,相互连接形成密集的立体网状结构,骨小梁表面胶原纤维走向清晰,排列紧密、整齐,纤维之间有斜向纤维,部分交织成网状。手术组皮质骨致密,骨小梁结构与对照组相似,骨小梁表面胶原纤维走向欠清晰,排列松散、杂乱,纤维之间有斜向纤维,部分交织成网状。假手术组结构与对照组相似。肉毒毒素组皮质骨致密,髁突部骨小梁数目较多,厚度不均,骨小梁的间隙略增大,相互连接形成立体网状结构,骨小梁表面胶原纤维纤细、排列紊乱,局部呈现交织的网状结构。
6.免疫组化结果：手术组、假手术组、肉毒毒素组和对照组的成骨细胞、骨细胞、破骨细胞均未见IL-6、TNF-a的阳性表达。
7.下颌骨骨密度：各组左、右两侧下颌骨骨密度比较差异无统计学意义；各组右侧下颌骨骨密度与对照组比较差异无统计学意义。
8.有限元分析：建立了手术组、肉毒毒素组和对照组下颌骨的三维有限元模型。肉毒毒素组下颌支的最大应力(630.5MPa)与最大应变(1.847)小于对照组,最大位移(2.466mm)小于对照组(3.306mm)。肉毒毒素组下颌角的最大应力(66.4MPa)与最大应变(0.2278)大于对照组,最大位移为7.508mm,高于对照组。手术组下颌支、下颌角的各项结果在数值上与对照组接近。
结论
1.切除幼龄大鼠的咬肌神经,大鼠成年后下颌骨长度和下颌骨高度Ⅰ无明显改变；下颌骨高度Ⅱ和下颌间距较正常减小。下颌骨皮质骨、松质骨的组织学结构基本正常,骨小梁表面胶原纤维排列松散、杂乱,仍交织成网状。下颌骨的骨密度未发生明显变化。有限元分析可见：下颌支、下颌角两个部位的最大应力、最大应变和受最大外力时发生的最大位移数值上与对照组接近,说明咬肌神经切除后下颌骨抵抗弹性变形的生物力学性能未发生明显改变。
2.对幼龄大鼠的咬肌注射A型肉毒毒素,大鼠成年后下颌骨长度、下颌骨高度Ⅰ和下颌间距无明显改变；下颌骨高度Ⅱ和下颌骨高度Ⅲ较正常减小。下颌骨皮质骨致密,髁突软骨发育欠佳,骨小梁表面胶原纤维排列紊乱,不呈现明显的网状结构。下颌骨的骨密度未发生明显变化。有限元分析可见：下颌支的最大应力、最大应变和最大位移均小于对照组。下颌角的最大应力与最大应变大于对照组,受最大外力时发生的最大位移高于对照组。说明注射A型肉毒毒素后下颌角抵抗弹性变形的生物力学性能有所降低。
本研究的创新之处在于：同时完整地建立了咬肌神经切除和化学去神经的动物模型,通过CT三维重建,系统、详细地测量了下颌骨的三维形态数据,克服了以往的X线头影测量等的局限,能在三维空间测量下颌间距；对下颌骨的组织学结构、超微结构进行了详细观察,并测量了骨密度,为下颌骨的生物力学分析提供合理的理论支持；利用近年发展的有限元方法作为研究手段,所得结果更精确,克服了下颌骨标本小,不易直接行生物力学测试的缺陷。
总之,虽然咬肌神经切除术和咬肌肌内注射A型肉毒毒素未广泛应用于临床治疗相关疾病,但整形美容外科的发展趋势迫切需要相关的基础研究。本研究为咬肌神经切除和化学去神经的操作安全性、疗效预测、并发症等方面提供了一定的参考。
Background
Facial contour plasty has become one of the hot spots of plastic surgery with the development of craniofacial surgery these years. Prominent mandibular angle and masseteric hypertrophy is the most popular defect of the facial contour of the oriental nations. Mini-invasive technique is now the new trend of treatment for prominent mandibular angle and masseteric hypertrophy with the improvement of minimal invasive surgery and non-surgical cosmetic techniques, such as denervation of masseter muscle, radiofrequency volumetric reduction of masseter muscle, injection of botulinum toxin type A to the masseter muscle, etc. Hwang firstly reported four cases of selective neurectomy of masseteric nerve in 2004. Moore used botulinum toxin type A to treat masseteric hypertrophy in 1994. After that, excellent results were seen using domestic-made botulinum toxin type A to treat masseteric hypertrophy in China.
The growth and development of mandible is a continual process. The growth and remodeling of the mandible depends on the balance between bone deposition and bone resorption, especially during the adolescent age. With the development of plastic and cosmetic surgery, plastic and cosmetic operations are safe now and there are very few significant complications. Attitudes about plastic and aesthetic surgery have changed over the past ten years. An increasing number of patients undergo plastic and cosmetic procedures every year. The number of teenagers choosing to have cosmetic procedures is increasing at a rapid rate during these years. The merits such as simple, short time, mini-invasion and rapid recovery of minimal invasive and non-surgical cosmetic techniques attract more and more teenagers. But new problems of facial contour surgery arise due to the succession of growth and development of mandible and the increasing teenagers. If denervation and chemodenervation are performed before puberty, are there any influences of the mandible during the adolescent age? What changes will occur to the mandibular morphology, histology, ultramicrostructures, BMD and biomechanics properties? Studies are urgently needed to solve these problems before widespread clinical apply of these mini-invasive techniques.
Objective
The objective of this study is to evaluate the effect of denervation and chemodenervation (injection of botulinum toxin type A) of masseter muscle on the growth and development of mandible. Animal models of denervation and chemodenervation of masseter muscle are established before puberty. In the denervation group, one side of the masseteric nerve is severed by microsurgery procedure. While botulinum toxin type A is injected into one side of the masseter muscle in the chemodenervation group. When the animals grow up and maturity is attained, studies are as below:measurement of the mandibular length, mandibular height and bigonial width by 3D reconstructive technique; observation of histology and ultramicrostructures; measurement of the BMD of the mandible; biomechanical analysis of the mandible using finite element method. This preliminary study is aim for providing some available information about mandibular growth and development after denervation and chemodenervation of masseter muscle.
Method
1. Experimental animals and grouping:Thirty 21 days old male Wistar rats were randomly divided into four groups:operation group (9 rats), sham group (9 rats) botulinum toxin group (6 rats) and control group (6 rats)
2. Animal model of operation group and sham group:When the rats were 28 days old, the main trunk and initial branches of masseteric nerve on the right side were resected by microsurgery procedure in the operation group. The nerve was exposed, but not resected in the sham group.
3. Animal model of botulinum toxin group:When the rats were 28 days old, the right side of masseter muscle was injected with botulinum toxin type A (0.1ml,2U) and the left side was injected with sterile saline (0.1m) in the botulinum toxin group. The control group was only anaesthetised.
4. CT scan and anthropometric measurements:CT scan was taken when all rats were 75 days old. Bilateral mandibles were 3D reconstructed by PHILIPS Brilliance TM CT software. Seven cephalometric points were digitized as below:Cor (Coronoid point), Con (Condylion point), Go (Gonion point), GoT (Gonion tangent point), Ma (Mandibular alveolar point), Iia(Incisive inferior alveolar point), Me (Menton point). And selected seven linear distances were measured as below:Mandibular lengthⅠ(Cor-Iia), Mandibular lengthⅡ(Con-Iia), Mandibular lengthⅢ(Go-Iia), mandibular heightⅠ(Ma-Me), mandibular heightⅡ(Cor-GoT), mandibular heightⅢ(Con-GoT) and Bigonial width (GoT1-GoT2).
5. Measurement of the masseter muscles:The rats were killed with an overdose of 10% chloral hydrate after CT scan and anthropometric measurements. Masseter muscles of each side were integrallty obtained and weighted on electronic balance immediately.
6. Observation of histology, ultramicrostructures and IHC staining:Mandibles of each group were fixed with 4% paraformaldehyde solution for 1-2 hours and then were decalcified with 10% ethylene diamine tetra acetic acid (EDTA) for 3 weeks. HE staining was performed on the region of angle, ramus, and condyle of the mandible. Other mandibles of each group were washed with 0.1mmol/l phosphate buffered saline (PBS) and then were fixed with 2.5% glutaraldehyde solution for 24 hours. Dehydration, arescent at critical point and conductive coating were performed before observation with SEM. Some of the histological slides from each group were immunohistochemical stained. Reactions of the antibodies including IL-6 and TNF-a were analyzed in the mandible.
7. Measurement of BMD:Bilateral mandibles of all four groups were scanned by GE lunar prodigy bone densitometer. ROI was defined in the region where the masseter muscle attached. Then the results of BMD were calculated with the software of small animals (en CORE 2006 V10.50.086).
8. Finite element analysis:The DICOM files from the CT scan of the mandible were imported into Mimics. Preliminary mandibular 3D model was built after segmentation, thresholding, region growing and Calculate 3D. After the mandibular model was remeshed,3D tetrahedral network model of mandible was established by the software of MSC.Patran. According to the value of gray scale at different parts of the mandible from the CT sections in Mimics, the Elastic module can be obtained (maximum:1200MPa; minimum:1MPa). Poisson Ratio was 0.3. Then the three-points bending tests of mandibular ramus and mandibular angle were performed on the model using the software of MSC.Marc. The load of 200N was applied to the center of mandibular ramus and 10N was applied to the Gonion point. The load was exerted by ten steps in one second. FEA results included maximum equivalent Von Mises stress, maximum equivalent of total strain, maximum external force and maximum displacement.
9. Statistical analysis:Statistical analyses were carried out with SPSS 13.0. All measurement data were presented as means with standard deviations. The differences between the left and right side to each group were determined by paired samples t-test. The differences among groups were determined by independent samples t-test and one-way ANOVA, and multiple comparisons were determined using Fisher's least significant difference t-test. The significance level was set at P<0.05.
Results
1. General status:All of the rats in operation and sham group are live after surgery. Dead does not occurred. Lateral deviated occlusion is observed on two rats in botulinum toxin group. Gross appearance:significant atrophy on the right side can be seen in both operation group and botulinum toxin group. Bilateral masseter muscles were symmetric in sham group and control group.
2. Body weight and Quality of masseter muscle:Differences of the body weight between pre-operation and post-operation in operation group and sham group are not significant. Differences of the body weight between pre-injection and post-injection in botulinum toxin group and control group are not significant, except for the first week after injection. In the operation group, the quality of masseter muscle of the right side is less than that of the left side (P=0.000), and it is also less than that in sham group and control group. In the botulinum toxin group, the quality of masseter muscle of the right side is less than that of the left side (P=0.001); the quality of masseter muscle on both sides are less than that in control group (P=0.016、P=0.000)
3. Measurements of mandible
3.1 Operation group and sham group
(1) Comparison between two sides:Mandibular heightⅡ(12.0±0.3mm) and mandibular heightⅢ(9.4±0.4mm)of the right side are less than those of the left side (12.6±0.4mm,10.5±0.3mm, respectively) (P=0.001, P=0.000, respectively) in operation group. In sham group, mandibular heightⅢ(9.6±0.4mm) of the right side is less than that of the left side (10.6±0.4mm) (P=0.000)
(2) Comparisons of right side among groups:Differences of mandibular length and mandibular heightⅠamong groups are not significant. Mandibular heightⅡ(12.0±0.3mm) of operation group is less than that of control group (P=0.017) Mandibular heightⅢof operation group and sham group (9.4±0.4mm,9.6±0.4mm, respectively) are all less than those of control group (all, P=0.000)
(3) Comparisons of bigonial width:Bigonial width of operation group is less than that of control group (P=0.018)
3.2 Botulinum toxin group
(1) Comparison between two sides:Mandibular lengthⅢ(19.2±1.4mm) of the right side is less than that of the left side (20.4±1.4mm) (P=0.033). Mandibular heightⅡ(10.8±0.8mm) of the right side is less than that of the left side (12.0±0.9mm) (P=0.001)
(2) Comparisons of right side among groups:Differences of Mandibular length and mandibular heightⅠamong groups are not significant. Mandibular heightⅡ(10.8±0.8mm)and mandibular heightⅢ(9.5±0.6mm)of botulinum toxin group are less than those of control group (P=0.007, P=0.005, respectively)
(3) Comparisons of bigonial width:Bigonial width of botulinum toxin group is less than that of control group, but differences are not significant.
4. Histology:In operation group, sham group and control group, all mandibles have compact cortex, abundant bone trabecula and uniform distributed bone lacuna. The cortical bone of mandible in botulinum toxin group is also compact. But bone trabecula is not as abundant as that of control group. Distributions of bone lacunas are inhomogeneous. The condylar cartilage of control group is stained and delaminated clearly. Whereas the cellulous layers of cartilage are not conspicuous in botulinum toxin group.
5. Ultramicrostructures:The cortical bone of mandible in control group is compact. There are plenty of bone trabeculas on the condyle and thickness of them is uniform. A conferted 3D reticular structure is built by the bone trabeculas connecting to each other. Array of collagen fibers on the surface of trabecula are regular and compact. Parts of the fibers connect to each other forming a network. The ultramicrostructures of operation group and sham group is similar as that of control group. But array of collagen fibers are loose and irregular. In botulinum toxin group, thickness of bone trabecula is inhomogeneous. The interspaces among the trabeculas are a little wider. Array of collagen fibers are more irregular. The network of collagen fibers is only presented on partial region.
6. IHC staining:Positive reaction is not found on osteoblast, osteocyte and osteoclast in all the four groups.
7. BMD:Differences of the BMD between left and right side of mandible in all the four groups are not significant. Differences of the BMD on the right side of mandible among operation group, sham group, botulinum toxin group and control group are not significant.
8. Finite element analysis:3D-finite element model of mandible was established in operation group, botulinum toxin group and control group. In botulinum toxin group, maximum equivalent Von Mises stress (630.5MPa) and maximum equivalent of total strain (1.847) at mandibular ramus are less than those of control group. And maximum displacement (2.466mm) at mandibular ramus is also less than that of control group. At mandibular angle, maximum equivalent Von Mises stress (66.4MPa) and maximum equivalent of total strain (0.2278) are less than those of control group. But maximum displacement (7.508mm) is greater than that of control group. The results at mandibular ramus and mandibular angle of operation group are similar as those of control group.
Conclusion
1. After resection of the masseteric nerve of rat before puberty, alterations of mandibular length and mandibular heightⅠare not seen when the rat grow up and maturity is attained. Mandibular heightⅡand bigonial width are decreased. Histology of cortical and trabecular bone of mandible are generally normal. Array of collagen fibers on the surface of trabecula are loose and irregular, and collagen network can be seen. BMD of mandible is not changed. The maximum equivalent Von Mises stress, maximum equivalent of total strain and maximum displacement at mandibular ramus and mandibular angle are similar as those of control group. The biomechanical behaviour of resisting elastic deformation of the mandible is not changed after neurectomy of masseter muscle.
2. After injection of botulinum toxin type A to masseter muscle of rat before puberty, alterations of mandibular length, mandibular heightⅠand bigonial width are not seen when the rat grow up and maturity is attained. Mandibular heightⅡand mandibular heightⅢare decreased. The cortical bone of mandible is compact. The condylar cartilage is poorly developed. Array of collagen fibers on the surface of trabecula are more irregular. The network of collagen fibers is only presented on partial region. BMD of mandible is not changed. The maximum equivalent Von Mises stress, maximum equivalent of total strain and maximum displacement at mandibular ramus are less than those of control group. While the maximum equivalent Von Mises stress and maximum equivalent of total strain at mandibular angle are greater than those of control group. The biomechanical property of resisting elastic deformation of the mandible is not changed after neurectomy of masseter muscle. And displacement of the mandibular angle is greater than other groups. The biomechanical behaviour of resisting elastic deformation of the mandible is influenced by chemodenervation of masseter muscle. The strength of the mandibular angle is decreased.
There are several new ideas brought by this study. Firstly, the animal models of denervation and chemodenervation of masseter muscle are established simultaneously. Systematic anthropometric measurements of the mandible are performed by 3D reconstruction. The two-dimensional limitation of X-ray cephalometric measurements is eliminated. And the bigonial width can be measured in 3D space. Secondly, theoretical support can be afforded to the biomechanical study of mandible on base of observation of histology and measurement of BMD. Thirdly, the mandible of rat is too small to undergo biomechanical test. FEM is an alternative method and FEA can afford reliable results.
On the whole, although neurectomy of masseteric nerve and intramuscular injection of botulinum toxin type A are not extensively applied to improving facial contour, basic research is necessary for the development of plastic and cosmetic surgery. This study aims for affording available references about the safety, prediction of therapeutic effect and complications of denervation and chemodenervation of masseter muscle.
随着近年来颅颌面外科的发展,面部轮廓整形美容逐渐成为整形外科关注的热点之一。下颌角和咬肌肥大是东亚各民族常见的面部轮廓缺陷。随着微创外科和非手术整形美容技术的发展,下颌角和咬肌肥大的治疗也有向微侵袭技术发展的趋势,如咬肌去神经、射频消融等微创手术和A型肉毒毒素咬肌注射等非手术整形技术等。2004年Hwang首次报道了4例选择性咬肌神经切除术。1994年Moore应用A型肉毒毒素治疗咬肌肥大,2000年国内学者用国产肉毒毒素治疗咬肌肥大,收到了良好的治疗效果。
下颌骨的生长发育是一个连续的过程,通过调节骨沉积和骨吸收之间的平衡,下颌骨完成生长和重塑,青春期下颌骨的生长发育尤为重要。随着整形美容外科的发展,整形美容手术的安全性不断提高,并发症减少,逐渐在改变人们对整形美容的认知,越来越多的人寻求整形美容手术的帮助；求美者数量急剧增加的同时,求美者的年龄也呈现年轻化趋势,越来越多的青少年接受整形美容治疗。而微创技术和非手术整形美容技术由于非侵袭性、创伤小、恢复快、简单有效等优点更易使求美者呈现年轻化趋势。下颌骨生长发育的连续性和求美者的年轻化趋势,使面部轮廓整形美容面临新的问题：青春期前接受咬肌神经切除术或A型肉毒毒素咬肌注射,对青春期下颌骨的生长发育有无影响?对成年后下颌骨的形态、组织学、超微结构、骨密度、生物力学等方面产生怎样的影响?这些问题亟待在临床广泛应用之前进行深入研究和探讨。
目的
本研究拟对咬肌神经切除和化学去神经(咬肌注射A型肉毒毒素)后下颌骨的形态学、组织学、超微结构、骨密度、生物力学等方面的改变进行初步研究。实验分别切除幼龄大鼠一侧咬肌神经和在幼龄大鼠一侧咬肌肌内注射A型肉毒毒素,构建咬肌去神经和咬肌化学去神经的动物模型。待大鼠成年后,利用CT三维重建技术测量其下颌骨的长度、高度、下颌间距,对下颌骨进行组织学、超微结构的观察,测量下颌骨的骨密度,并利用有限元方法对下颌骨进行初步的生物力学分析,以期为咬肌神经切除和化学去神经后下颌骨的生物学研究提供参考。
方法
1.实验动物和分组：出生后21日龄断乳的雄性Wistar大鼠30只随机分成4组：手术组9只,切除右侧咬肌神经；假手术组9只,显露但不切除右侧咬肌神经；肉毒毒素组6只,右侧咬肌肌内注射A型肉毒毒素,左侧咬肌肌内注射生理盐水；对照组6只,仅将大鼠麻醉。
2.手术组、假手术组动物模型的建立：大鼠28日龄时进行实验,显微外科操作暴露咬肌神经主干及其分支,切断2-3 mm咬肌神经主干及部分分支。假手术组仅暴露右侧咬肌神经,不切除。
3.肉毒毒素组动物模型的建立：大鼠28日龄时进行实验,向右侧咬肌浅、深层各注射A型肉毒毒素0.05ml,共0.1ml即2U,向左侧咬肌浅、深层各注射生理盐水0.05ml,共0.1ml。
4.CT扫描和下颌骨测量：各组大鼠75日龄时,予10%水合氯醛腹腔注射麻醉后,行头颅CT平扫,用PHILIPS Brilliance TM CT工作站软件三维重建双侧下颌骨,确定测量标志点：Cor：冠突最上点；Con：髁突后上点；Go：下颌角后上点；GoT：下颌角最下点；Ma：下颌骨牙槽嵴上缘最凹点；Iia：下颌中切牙牙槽骨前下点；Me：下颌联合最下点。测量相关标志点间的线距：①下颌骨长度：下颌骨长度Ⅰ(Cor-Iia)、下颌骨长度Ⅱ(Con-Iia)、下颌骨长度Ⅲ(Go-Iia)。②下颌骨高度：下颌骨高度Ⅰ(Ma-Me)、下颌骨高度Ⅱ(Cor-GoT)、下颌骨高度Ⅲ(Con-GoT)。③下颌间距(GoT1-GoT2)
5.称量咬肌质量：CT扫描、测量完成后,各组大鼠予过量水合氯醛麻醉致死,完整切取双侧咬肌,迅速用电子天平称取新鲜咬肌质量并记录。
6.组织学、超微结构、免疫组化染色观察：取各组大鼠完整下颌骨,用4%多聚甲醛溶液固定1-2小时后,予10%EDTA溶液脱钙3周,取下颌角区、下颌体部、髁突各5mm×5mm大小骨组织,HE染色后行组织学观察；各组下颌骨标本用0.1mmol/1的PBS缓冲液冲洗后,用2.5%戊二醛溶液4℃固定24小时,经脱水、临界点干燥、真空喷金镀膜后行超微结构观察；组织白片行IL-6、TNF-α免疫组化染色,观察IL-6、TNF-α在下颌骨组织中的表达。
7.骨密度测量：取各组双侧完整下颌骨,利用en CORE 2006 V10.50.086分析软件中的小动物软件,在双能X线骨密度仪下测量感兴趣区的骨密度,兴趣区界定为咬肌附着区域。
8.有限元分析：将CT扫描获得的DICOM数据文件导入Mimics软件,行图像分割、阈值分割、区域增长、Calculate 3D后生成初步的下颌骨三维模型。用Mimics中FEA模块的Remesh功能,对三维模型进行表面优化和修洁处理。利用MSC.Patran软件,创建实体单元,生成四面体实体网格模型。根据Mimics中CT断层图像的大鼠下颌骨各部位的灰度值,计算求得最大弹性模量1200MPa,最小弹性模量1MPa,泊松比设为0.3。采用MSC.Marc软件对下颌支和下颌角行有限元分析,模拟三点弯曲试验。下颌支施加载荷点为下颌支的中心点,施加200N的力；下颌角施加载荷点为下颌角后上点,施加1ON的力。设置载荷在1秒内分10步完成,求解下颌支、下颌角的最大应力、最大应变、最大外力、最大位移。
9.统计学分析：采用SPSS 13.0统计软件分析,实验数据的计量资料以均数±标准差(x±s)表示,组内左、右侧的比较用配对t检验,组间比较用独立样本t检验和单因素方差分析,多重比较用LSD-t检验,以P<0.05为差异有统计学意义。
结果
1.一般情况：手术组、假手术组18只大鼠全部成活,术后无死亡。肉毒毒素组有2只大鼠发生偏颌。大体观察：手术组右侧咬肌萎缩,肉毒毒素组右侧咬肌明显萎缩,假手术组、对照组双侧咬肌饱满。
2.体重和咬肌质量：手术组、假手术组术前和术后体重差异无统计学意义。除注射后第1周,肉毒毒素组体重小于对照组外,注射前、后肉毒毒素组和对照组体重差异无统计学意义。手术组右侧咬肌质量小于左侧(P=0.000)；右侧咬肌质量小于假手术组和对照组(均P<0.05)。肉毒毒素组右侧咬肌质量小于左侧(P=0.001)；左、右两侧咬肌质量均小于对照组(P=0.016、P=0.000)。
3.下颌骨测量结果：
3.1手术组、假手术组
(1)组内左、右两侧比较：手术组右侧下颌骨高度Ⅱ(12.0±0.3mm)、下颌骨高度Ⅲ(9.4±0.4mm)小于左侧(分别为12.6±0.4mm.10.5±0.3mm)(P分别为P=0.001、P=0.000),假手术组右侧下颌骨高度Ⅲ(9.6±0.4mm)小于左侧(10.6±0.4mm)(P=0.000)。
(2)各组右侧线距的比较：下颌骨长度和下颌骨高度Ⅰ,各组之间差异无统计学意义。手术组下颌骨高度Ⅱ(12.0±0.3mm)小于对照组(P=0.017)。手术组、假手术组下颌骨高度Ⅲ(分别为9.4±0.4mm、9.6±0.4mm)小于对照组(均为P=0.000)。
(3)下颌间距比较：手术组小于对照组(P=0.018)。
3.2肉毒毒素组
(1)组内左、右两侧比较：肉毒毒素组右侧下颌骨长度Ⅲ(19.2±1.4mm)小于左侧(20.4±1.4mm),右侧下颌骨高度Ⅱ(10.8±0.8mm)小于左侧(12.0±0.9mm)(P分别为P=0.033、P=0.001)。
(2)右侧线距的比较：下颌骨长度和下颌骨高度Ⅰ肉毒毒素组与对照组比较,差异无统计学意义；肉毒毒素组下颌骨高度Ⅱ(10.8±0.8mm)、下颌骨高度Ⅲ(9.5±0.6mm)均小于对照组(P分别为P=0.007、P=0.005)。
(3)下颌间距：肉毒毒素组(11.6±0.6mm)小于对照组(12.4±0.6 mm),但差异无统计学意义。
4.组织学观察：手术组、假手术组、对照组下颌骨皮质骨致密,骨小梁丰富,骨陷窝大小、分布均一；肉毒毒素组下颌骨皮质骨致密,骨小梁欠丰富,骨陷窝大小、分布不均,部分骨细胞核细长。肉毒毒素组髁突软骨分层不明显,细胞染色较淡；对照组髁突软骨染色清晰,分层明显。
5.超微结构观察：对照组皮质骨致密,髁突部骨小梁数目较多,厚度较均匀,骨小梁的间隙较小,相互连接形成密集的立体网状结构,骨小梁表面胶原纤维走向清晰,排列紧密、整齐,纤维之间有斜向纤维,部分交织成网状。手术组皮质骨致密,骨小梁结构与对照组相似,骨小梁表面胶原纤维走向欠清晰,排列松散、杂乱,纤维之间有斜向纤维,部分交织成网状。假手术组结构与对照组相似。肉毒毒素组皮质骨致密,髁突部骨小梁数目较多,厚度不均,骨小梁的间隙略增大,相互连接形成立体网状结构,骨小梁表面胶原纤维纤细、排列紊乱,局部呈现交织的网状结构。
6.免疫组化结果：手术组、假手术组、肉毒毒素组和对照组的成骨细胞、骨细胞、破骨细胞均未见IL-6、TNF-a的阳性表达。
7.下颌骨骨密度：各组左、右两侧下颌骨骨密度比较差异无统计学意义；各组右侧下颌骨骨密度与对照组比较差异无统计学意义。
8.有限元分析：建立了手术组、肉毒毒素组和对照组下颌骨的三维有限元模型。肉毒毒素组下颌支的最大应力(630.5MPa)与最大应变(1.847)小于对照组,最大位移(2.466mm)小于对照组(3.306mm)。肉毒毒素组下颌角的最大应力(66.4MPa)与最大应变(0.2278)大于对照组,最大位移为7.508mm,高于对照组。手术组下颌支、下颌角的各项结果在数值上与对照组接近。
结论
1.切除幼龄大鼠的咬肌神经,大鼠成年后下颌骨长度和下颌骨高度Ⅰ无明显改变；下颌骨高度Ⅱ和下颌间距较正常减小。下颌骨皮质骨、松质骨的组织学结构基本正常,骨小梁表面胶原纤维排列松散、杂乱,仍交织成网状。下颌骨的骨密度未发生明显变化。有限元分析可见：下颌支、下颌角两个部位的最大应力、最大应变和受最大外力时发生的最大位移数值上与对照组接近,说明咬肌神经切除后下颌骨抵抗弹性变形的生物力学性能未发生明显改变。
2.对幼龄大鼠的咬肌注射A型肉毒毒素,大鼠成年后下颌骨长度、下颌骨高度Ⅰ和下颌间距无明显改变；下颌骨高度Ⅱ和下颌骨高度Ⅲ较正常减小。下颌骨皮质骨致密,髁突软骨发育欠佳,骨小梁表面胶原纤维排列紊乱,不呈现明显的网状结构。下颌骨的骨密度未发生明显变化。有限元分析可见：下颌支的最大应力、最大应变和最大位移均小于对照组。下颌角的最大应力与最大应变大于对照组,受最大外力时发生的最大位移高于对照组。说明注射A型肉毒毒素后下颌角抵抗弹性变形的生物力学性能有所降低。
本研究的创新之处在于：同时完整地建立了咬肌神经切除和化学去神经的动物模型,通过CT三维重建,系统、详细地测量了下颌骨的三维形态数据,克服了以往的X线头影测量等的局限,能在三维空间测量下颌间距；对下颌骨的组织学结构、超微结构进行了详细观察,并测量了骨密度,为下颌骨的生物力学分析提供合理的理论支持；利用近年发展的有限元方法作为研究手段,所得结果更精确,克服了下颌骨标本小,不易直接行生物力学测试的缺陷。
总之,虽然咬肌神经切除术和咬肌肌内注射A型肉毒毒素未广泛应用于临床治疗相关疾病,但整形美容外科的发展趋势迫切需要相关的基础研究。本研究为咬肌神经切除和化学去神经的操作安全性、疗效预测、并发症等方面提供了一定的参考。
Background
Facial contour plasty has become one of the hot spots of plastic surgery with the development of craniofacial surgery these years. Prominent mandibular angle and masseteric hypertrophy is the most popular defect of the facial contour of the oriental nations. Mini-invasive technique is now the new trend of treatment for prominent mandibular angle and masseteric hypertrophy with the improvement of minimal invasive surgery and non-surgical cosmetic techniques, such as denervation of masseter muscle, radiofrequency volumetric reduction of masseter muscle, injection of botulinum toxin type A to the masseter muscle, etc. Hwang firstly reported four cases of selective neurectomy of masseteric nerve in 2004. Moore used botulinum toxin type A to treat masseteric hypertrophy in 1994. After that, excellent results were seen using domestic-made botulinum toxin type A to treat masseteric hypertrophy in China.
The growth and development of mandible is a continual process. The growth and remodeling of the mandible depends on the balance between bone deposition and bone resorption, especially during the adolescent age. With the development of plastic and cosmetic surgery, plastic and cosmetic operations are safe now and there are very few significant complications. Attitudes about plastic and aesthetic surgery have changed over the past ten years. An increasing number of patients undergo plastic and cosmetic procedures every year. The number of teenagers choosing to have cosmetic procedures is increasing at a rapid rate during these years. The merits such as simple, short time, mini-invasion and rapid recovery of minimal invasive and non-surgical cosmetic techniques attract more and more teenagers. But new problems of facial contour surgery arise due to the succession of growth and development of mandible and the increasing teenagers. If denervation and chemodenervation are performed before puberty, are there any influences of the mandible during the adolescent age? What changes will occur to the mandibular morphology, histology, ultramicrostructures, BMD and biomechanics properties? Studies are urgently needed to solve these problems before widespread clinical apply of these mini-invasive techniques.
Objective
The objective of this study is to evaluate the effect of denervation and chemodenervation (injection of botulinum toxin type A) of masseter muscle on the growth and development of mandible. Animal models of denervation and chemodenervation of masseter muscle are established before puberty. In the denervation group, one side of the masseteric nerve is severed by microsurgery procedure. While botulinum toxin type A is injected into one side of the masseter muscle in the chemodenervation group. When the animals grow up and maturity is attained, studies are as below:measurement of the mandibular length, mandibular height and bigonial width by 3D reconstructive technique; observation of histology and ultramicrostructures; measurement of the BMD of the mandible; biomechanical analysis of the mandible using finite element method. This preliminary study is aim for providing some available information about mandibular growth and development after denervation and chemodenervation of masseter muscle.
Method
1. Experimental animals and grouping:Thirty 21 days old male Wistar rats were randomly divided into four groups:operation group (9 rats), sham group (9 rats) botulinum toxin group (6 rats) and control group (6 rats)
2. Animal model of operation group and sham group:When the rats were 28 days old, the main trunk and initial branches of masseteric nerve on the right side were resected by microsurgery procedure in the operation group. The nerve was exposed, but not resected in the sham group.
3. Animal model of botulinum toxin group:When the rats were 28 days old, the right side of masseter muscle was injected with botulinum toxin type A (0.1ml,2U) and the left side was injected with sterile saline (0.1m) in the botulinum toxin group. The control group was only anaesthetised.
4. CT scan and anthropometric measurements:CT scan was taken when all rats were 75 days old. Bilateral mandibles were 3D reconstructed by PHILIPS Brilliance TM CT software. Seven cephalometric points were digitized as below:Cor (Coronoid point), Con (Condylion point), Go (Gonion point), GoT (Gonion tangent point), Ma (Mandibular alveolar point), Iia(Incisive inferior alveolar point), Me (Menton point). And selected seven linear distances were measured as below:Mandibular lengthⅠ(Cor-Iia), Mandibular lengthⅡ(Con-Iia), Mandibular lengthⅢ(Go-Iia), mandibular heightⅠ(Ma-Me), mandibular heightⅡ(Cor-GoT), mandibular heightⅢ(Con-GoT) and Bigonial width (GoT1-GoT2).
5. Measurement of the masseter muscles:The rats were killed with an overdose of 10% chloral hydrate after CT scan and anthropometric measurements. Masseter muscles of each side were integrallty obtained and weighted on electronic balance immediately.
6. Observation of histology, ultramicrostructures and IHC staining:Mandibles of each group were fixed with 4% paraformaldehyde solution for 1-2 hours and then were decalcified with 10% ethylene diamine tetra acetic acid (EDTA) for 3 weeks. HE staining was performed on the region of angle, ramus, and condyle of the mandible. Other mandibles of each group were washed with 0.1mmol/l phosphate buffered saline (PBS) and then were fixed with 2.5% glutaraldehyde solution for 24 hours. Dehydration, arescent at critical point and conductive coating were performed before observation with SEM. Some of the histological slides from each group were immunohistochemical stained. Reactions of the antibodies including IL-6 and TNF-a were analyzed in the mandible.
7. Measurement of BMD:Bilateral mandibles of all four groups were scanned by GE lunar prodigy bone densitometer. ROI was defined in the region where the masseter muscle attached. Then the results of BMD were calculated with the software of small animals (en CORE 2006 V10.50.086).
8. Finite element analysis:The DICOM files from the CT scan of the mandible were imported into Mimics. Preliminary mandibular 3D model was built after segmentation, thresholding, region growing and Calculate 3D. After the mandibular model was remeshed,3D tetrahedral network model of mandible was established by the software of MSC.Patran. According to the value of gray scale at different parts of the mandible from the CT sections in Mimics, the Elastic module can be obtained (maximum:1200MPa; minimum:1MPa). Poisson Ratio was 0.3. Then the three-points bending tests of mandibular ramus and mandibular angle were performed on the model using the software of MSC.Marc. The load of 200N was applied to the center of mandibular ramus and 10N was applied to the Gonion point. The load was exerted by ten steps in one second. FEA results included maximum equivalent Von Mises stress, maximum equivalent of total strain, maximum external force and maximum displacement.
9. Statistical analysis:Statistical analyses were carried out with SPSS 13.0. All measurement data were presented as means with standard deviations. The differences between the left and right side to each group were determined by paired samples t-test. The differences among groups were determined by independent samples t-test and one-way ANOVA, and multiple comparisons were determined using Fisher's least significant difference t-test. The significance level was set at P<0.05.
Results
1. General status:All of the rats in operation and sham group are live after surgery. Dead does not occurred. Lateral deviated occlusion is observed on two rats in botulinum toxin group. Gross appearance:significant atrophy on the right side can be seen in both operation group and botulinum toxin group. Bilateral masseter muscles were symmetric in sham group and control group.
2. Body weight and Quality of masseter muscle:Differences of the body weight between pre-operation and post-operation in operation group and sham group are not significant. Differences of the body weight between pre-injection and post-injection in botulinum toxin group and control group are not significant, except for the first week after injection. In the operation group, the quality of masseter muscle of the right side is less than that of the left side (P=0.000), and it is also less than that in sham group and control group. In the botulinum toxin group, the quality of masseter muscle of the right side is less than that of the left side (P=0.001); the quality of masseter muscle on both sides are less than that in control group (P=0.016、P=0.000)
3. Measurements of mandible
3.1 Operation group and sham group
(1) Comparison between two sides:Mandibular heightⅡ(12.0±0.3mm) and mandibular heightⅢ(9.4±0.4mm)of the right side are less than those of the left side (12.6±0.4mm,10.5±0.3mm, respectively) (P=0.001, P=0.000, respectively) in operation group. In sham group, mandibular heightⅢ(9.6±0.4mm) of the right side is less than that of the left side (10.6±0.4mm) (P=0.000)
(2) Comparisons of right side among groups:Differences of mandibular length and mandibular heightⅠamong groups are not significant. Mandibular heightⅡ(12.0±0.3mm) of operation group is less than that of control group (P=0.017) Mandibular heightⅢof operation group and sham group (9.4±0.4mm,9.6±0.4mm, respectively) are all less than those of control group (all, P=0.000)
(3) Comparisons of bigonial width:Bigonial width of operation group is less than that of control group (P=0.018)
3.2 Botulinum toxin group
(1) Comparison between two sides:Mandibular lengthⅢ(19.2±1.4mm) of the right side is less than that of the left side (20.4±1.4mm) (P=0.033). Mandibular heightⅡ(10.8±0.8mm) of the right side is less than that of the left side (12.0±0.9mm) (P=0.001)
(2) Comparisons of right side among groups:Differences of Mandibular length and mandibular heightⅠamong groups are not significant. Mandibular heightⅡ(10.8±0.8mm)and mandibular heightⅢ(9.5±0.6mm)of botulinum toxin group are less than those of control group (P=0.007, P=0.005, respectively)
(3) Comparisons of bigonial width:Bigonial width of botulinum toxin group is less than that of control group, but differences are not significant.
4. Histology:In operation group, sham group and control group, all mandibles have compact cortex, abundant bone trabecula and uniform distributed bone lacuna. The cortical bone of mandible in botulinum toxin group is also compact. But bone trabecula is not as abundant as that of control group. Distributions of bone lacunas are inhomogeneous. The condylar cartilage of control group is stained and delaminated clearly. Whereas the cellulous layers of cartilage are not conspicuous in botulinum toxin group.
5. Ultramicrostructures:The cortical bone of mandible in control group is compact. There are plenty of bone trabeculas on the condyle and thickness of them is uniform. A conferted 3D reticular structure is built by the bone trabeculas connecting to each other. Array of collagen fibers on the surface of trabecula are regular and compact. Parts of the fibers connect to each other forming a network. The ultramicrostructures of operation group and sham group is similar as that of control group. But array of collagen fibers are loose and irregular. In botulinum toxin group, thickness of bone trabecula is inhomogeneous. The interspaces among the trabeculas are a little wider. Array of collagen fibers are more irregular. The network of collagen fibers is only presented on partial region.
6. IHC staining:Positive reaction is not found on osteoblast, osteocyte and osteoclast in all the four groups.
7. BMD:Differences of the BMD between left and right side of mandible in all the four groups are not significant. Differences of the BMD on the right side of mandible among operation group, sham group, botulinum toxin group and control group are not significant.
8. Finite element analysis:3D-finite element model of mandible was established in operation group, botulinum toxin group and control group. In botulinum toxin group, maximum equivalent Von Mises stress (630.5MPa) and maximum equivalent of total strain (1.847) at mandibular ramus are less than those of control group. And maximum displacement (2.466mm) at mandibular ramus is also less than that of control group. At mandibular angle, maximum equivalent Von Mises stress (66.4MPa) and maximum equivalent of total strain (0.2278) are less than those of control group. But maximum displacement (7.508mm) is greater than that of control group. The results at mandibular ramus and mandibular angle of operation group are similar as those of control group.
Conclusion
1. After resection of the masseteric nerve of rat before puberty, alterations of mandibular length and mandibular heightⅠare not seen when the rat grow up and maturity is attained. Mandibular heightⅡand bigonial width are decreased. Histology of cortical and trabecular bone of mandible are generally normal. Array of collagen fibers on the surface of trabecula are loose and irregular, and collagen network can be seen. BMD of mandible is not changed. The maximum equivalent Von Mises stress, maximum equivalent of total strain and maximum displacement at mandibular ramus and mandibular angle are similar as those of control group. The biomechanical behaviour of resisting elastic deformation of the mandible is not changed after neurectomy of masseter muscle.
2. After injection of botulinum toxin type A to masseter muscle of rat before puberty, alterations of mandibular length, mandibular heightⅠand bigonial width are not seen when the rat grow up and maturity is attained. Mandibular heightⅡand mandibular heightⅢare decreased. The cortical bone of mandible is compact. The condylar cartilage is poorly developed. Array of collagen fibers on the surface of trabecula are more irregular. The network of collagen fibers is only presented on partial region. BMD of mandible is not changed. The maximum equivalent Von Mises stress, maximum equivalent of total strain and maximum displacement at mandibular ramus are less than those of control group. While the maximum equivalent Von Mises stress and maximum equivalent of total strain at mandibular angle are greater than those of control group. The biomechanical property of resisting elastic deformation of the mandible is not changed after neurectomy of masseter muscle. And displacement of the mandibular angle is greater than other groups. The biomechanical behaviour of resisting elastic deformation of the mandible is influenced by chemodenervation of masseter muscle. The strength of the mandibular angle is decreased.
There are several new ideas brought by this study. Firstly, the animal models of denervation and chemodenervation of masseter muscle are established simultaneously. Systematic anthropometric measurements of the mandible are performed by 3D reconstruction. The two-dimensional limitation of X-ray cephalometric measurements is eliminated. And the bigonial width can be measured in 3D space. Secondly, theoretical support can be afforded to the biomechanical study of mandible on base of observation of histology and measurement of BMD. Thirdly, the mandible of rat is too small to undergo biomechanical test. FEM is an alternative method and FEA can afford reliable results.
On the whole, although neurectomy of masseteric nerve and intramuscular injection of botulinum toxin type A are not extensively applied to improving facial contour, basic research is necessary for the development of plastic and cosmetic surgery. This study aims for affording available references about the safety, prediction of therapeutic effect and complications of denervation and chemodenervation of masseter muscle.
引文
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