咬肌及顳肌注射肉毒桿菌神經毒素之後對大屬顱顏生長發育之影響

Evaluation of Craniofacial Growth and Development Following Injections of Botulinum Neurotoxin into Masseter and Temporalis Muscles of Rats

邱琬棋(Wan Chi Chiu)

指導教授 ： 蔡吉陽

共同指導教授 ： 楊良友(Liang Yo Yang)

臺北醫學大學/口腔醫學院/牙醫學系碩博士班/碩士(2007年)

摘要

本研究目的是藉由將肉毒桿菌神經毒素A型 (Botox®, Allergan Pharmaceuticals, Irvine, CA, USA) 注入大鼠咬肌及顳肌，使咬肌和顳肌麻痺、萎縮，來探討咬肌和顳肌對顱顏生長發育之影響。研究方法是選取60隻28天大的Long-Evans雄性之大鼠，隨機分為四組，每組15隻，依部位將25U/mL的A型肉毒桿菌神經毒素(BoNT/A)注射於大鼠：Group I之雙側咬肌(雙側顳肌則施打等量之0.9%生理食鹽水)；Group II之雙側顳肌(雙側咬肌則施打等量之0.9%生理食鹽水)；Group III之雙側咬肌和顳肌；Group IV為對照組，雙側咬肌及顳肌只施打0.9%生理食鹽水。每星期一次，連續七週，測量老鼠之體重。而後將77天大的大鼠犧牲，取下咬肌和顳肌，測量其重量及量測乾燥頭顱骨大小(共40項測量項目)。
最後完成研究總計有53隻大鼠。結果發現四組的平均體重在七個星期中並無明顯之統計上的差異。顳肌平均重量Group I和Group IV(µ=0.64±0.03g和0.061±0.09g)較Group II及Group III(分別為µ=0.43±0.03g和0.33±0.02g)大；咬肌平均重量Group II和Group IV(分別為µ=1.41±0.07g和1.38±0.04g)較Group I及Group III(分別為µ=1.26±0.07g和1.04±0.04g)大。肌肉之平均重量具統計上的差異(p＜0.001)。乾燥頭顱骨的40項測量中，16項具有統計意義(p＜0.05)，分別為：(1)頭顱向實驗組之maximum skull height及upper anterior facial height比對照組小、lower anterior facial height和total anterior facial height比對照組大。(2)上顎向之U8 bimolar distance在Group III是最大的，而對照組是最小的。(3)下顎向測量項目中之total mandibular length I~III及corpus length實驗組較對照組大，而Group III是最大的；在ramus height I~IV方面，實驗組較對照組大，而Group I是最大的；在 mandibular plane angle方面實驗組比對照組平坦，且Group III的角度是最小的；在 bicoronoidal width和 bigonial width中，實驗組左右寬度較對照組小，而Group III是最小的。
本研究結果顯示咀嚼肌痲痺、萎縮且功能降低後會造成生長發育偏向垂直方向生長形成長臉型之顏面外觀。上臉部顯得矮短而下臉部變長，下顎骨體長度及下顎枝後緣高度也比正常大，下顎冠狀突及下顎骨角左右之間的距離也呈現狹窄之現象。研究證實了咀嚼肌萎縮後確實會影響顱顏骨型態及生長發育。

關鍵字

肉毒桿菌神經毒素 ； 顱顏生長發育

並列摘要

This study seeks to evaluate the craniofacial growth and development of growing rats following injections of botulinum neurotoxin type A (Botox®, Allergan Pharmaceuticals, Irvine, CA, USA) into masseter and temporalis muscles of rats. It aims to achieve masseter and temporalis muscle paralysis, inducing a decreased masticatory function, and to investigate the influences of masticatory hypofunction on cranial, maxillary, and mandibular bone growth and development.
The study was comprised of 60 Long-Evans rats which were 28 days old and randomly divided into four groups. A 25U/mL of botulinum neurotoxin type A (BoNT/A) was injected according to the following groups: Group I injection of bilateral masseter muscles (bilateral temporalis muscles received equal amounts of 0.9% sterile, non-preserved saline); Group II injection of bilateral temporalis muscles (bilateral masseter muscles received equal amounts of 0.9% sterile, non-preserved saline); Group III injection of bilateral masseter and temporalis muscles; Group IV is the control, both bilateral masseter and temporalis muscles received 0.9% sterile, non-preserved saline. The animals were weighed every week for a period of 7 consecutive weeks. After 49 days, the mature rats were perfused and sacrificed. The masseter and temporalis muscles were carefully dissected and harvested and the mean muscle mass were recorded. With the preparation of the dried skulls, direct anthropometric cranial, maxillary, and mandibular measurements (a total of 40 parameters) were carried out on the dried skulls.
At the end of the experiment, 53 animals completed the study. The mean changes in animal weights over the 7 weeks did not show any statistical significance. Following injections of BoNT-A, the mean temporalis mass in Group I and Group IV(µ=0.64±0.03g and 0.61±0.09g respectively) were more than Group II and Group III(µ=0.43±0.03g and 0.33±0.02g respectively); the mean masseter muscle mass in Group II and Group IV(µ=1.41±0.07g and 1.38±0.04 g) were more than Group I and Group III(µ=1.26±0.22g and 1.04±0.04g respectively). The differences in mean muscle wet mass were statistically significant (p＜0.001). Out of the 40 parameters measured, 16 direct anthropometric measurements were statistically significant(p＜0.05) and were as follows: (1)The cranial measurements in the experimental groups were smaller in the maximum skull height and upper anterior facial height and longer in the lower anterior facial height and the total anterior facial height. (2)The maxillary measurements of U8 bimolar distance were the widest in Group III and the narrowest in the control. (3)The mandibular measurements of total mandibular length I~III and the corpus length were longer in the experimental groups with the longest in Group III; in ramus height I~IV, the experimental groups were shorter than the control and Group I had the longest ramus height of all; the mandibular plane angles were flatter in the experimental groups and Group III had the smallest angle of all; in the bicoronoidal width and the bigonial width, the narrowest was in Group III.
The results shown that, following paralysis and atrophy of the masticatory muscles, a short upper anterior facial height with a lengthy lower anterior facial height would be observed. The mandibular length and the ramus height would be longer than normal and the distance between the right and left coronoid processes and the gonial angles would be shorter in width. This is typical of a facial profile that favors a vertical growth rotation and a formulation of dolichofacial pattern. It is demonstrated that atrophy of masitcatory muscles would alter craniofacial growth and development.

並列關鍵字

boutulinum neurotoxin ； craniofacial growth and development

參考文獻

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