成鼠咬肌注射肉毒桿菌神經毒素後的肌功能變化

Changes of masseter muscle function following injection of botulium toxin in adult rats

雷詠堯(Yung-Yao Lei)

指導教授 ： 蔡吉陽

共同指導教授 ： 楊良友

臺北醫學大學/口腔醫學院/牙醫學系碩博士班/碩士(2009年)

https://doi.org/10.6831/TMU.2009.00096

摘要

<研究目的>：近幾年已有許多研究將肉毒桿菌神經毒素運用在美容醫學的範疇，其中與齒顎矯正學科相關的，就是利用肉毒桿菌素治療咬肌肥大的病例。咬肌發達的患者常伴隨著方臉型以及前牙齒列深咬的發生，現今可經由注射肉毒桿菌素，造成咬肌萎縮，藉以影響下顎骨型態及深咬的改正。然而，施打肉毒桿菌素於咬肌，是否會造成咬肌功能實質的影響與變化則少見於以往的研究。因此，本實驗將藉由肌電圖的測量，實際量化比較肉毒桿菌素注射前後，成鼠咬肌功能之變化，以及肉毒桿菌神經毒素不同劑量對於咬肌功能
之影響程度。<材料和方法>：本實驗以肉毒桿菌素A型（Botox ® ,Allergan Inc.,Irvine,OCA,USA）(簡稱：BTXA) 注射大白鼠成鼠之咬肌，造成咬肌型態萎縮，藉肌電圖觀察肉毒桿菌神經毒素對成鼠咬肌肌肉功能之實際影響。實驗所採取的研究方式為：選取52隻十週大的大鼠（Wistar），隨機分成四組，其中三組為實驗組，另外一組為控制組。首先，對四組成鼠進行雙側咬肌電極線包埋手術，待手術復原一週後，固定每日餵食時間，並於每日餵食時間內頭一個小時測量咬肌之肌電圖訊號。記錄咬肌肌電訊號兩週後，依據不同實驗組別注射不同劑量之肉毒桿菌神經毒素（實驗組）及生理食鹽水（控制組）：Group I：右側咬肌注射BTXA 7.5 u (0.3ml)，左側咬肌注射入等量NaCl 0.3ml。Group II：右側咬肌注射BTXA 5.0 u (0.3ml)，左側咬肌注射入等量NaCl 0.3ml。Group III：右側咬肌注射BTXA 2.5 u (0.3ml)，左側咬肌注射入等量NaCl 0.3ml。Group IV（對照組）：雙側咬肌注射等量NaCl 0.3ml。待藥劑注射一週後，於每日餵食時間內，頭一個小時測量咬肌之肌電圖訊號。連續記錄肌電活動約3個月後，將大鼠麻醉犧牲，比較四組之間咬肌重量之差異，並分析咬肌肌電圖之變化。<實驗結果>：(1)總體而言， Group I, II, III 右側咬肌活動各項變數在BTXA注射後一週時，均下降超過90%(平均頻率除外)，且為咬肌活動記錄其間的最低狀態 (2)Group I和Group II右側咬肌活動約從注射BTXA後第4~6週開始有回復現象，Group III則約從注射BTXA後第3~4週開始有回復現象，開始回復後至注射BTXA後第12週，咬肌活動呈現平緩而線性增加。(3)注射後第12週，Group I 和Group II咬肌最大咬力振幅(RMS amplitude)回復至注射前的28%~33% ;而Group III則回復至注射前的55 % (4)控制組Group IV，各項咬肌活動變數在生理食鹽水注射前後沒有顯著的差異。<實驗結論>：(1)藉由將BTXA注射於大鼠成鼠之咬肌，咬肌的重量 以及進食時活動程度會明顯地降低。(2) 隨著注射BTXA劑量的增加，BTXA側咬肌肌肉活動被抑制的情形也會越顯著；然而當BTXA劑量超過5.0 u時，則影響的程度並沒有顯著的差異。 (3) 在Group I，Group II和Group III，即使到了注射後第十二週，BTXA側咬肌肌肉活動被抑制的情形仍舊存在。即使是實驗組的最低劑量（Group III：2.5 u BTXA），注射後第十二週時BTXA側咬肌的活動程度仍舊未回到注射前的狀態，且與注射前仍然存在著顯著差異。

關鍵字

咬肌 ； 肉毒桿菌神經毒素 ； 肌電圖

並列摘要

This study was designed to investigate the changes of masseter muscle function before and after intramuscular injection of botulium toxin type A (BTXA), and to compare the different extent of resultant changes as different dosage was used. Fifty-two male Wistar rats, 70-days old, were randomly divided into 4 groups. First of all, a wire-electrodes device was implanted for recording masseter muscle activity. One week after surgery, the rats were limited their oral feeding time within 2 hours daily, and EMG signals from masseter muscles were recorded when rats ingested pellets during the first hour .After EMG recording for 2 weeks, different dosage of BTXA was injected into R’t masseter muscle according to different groups : Group I-injection of 7.5u BTXA(0.3ml) into R’t masseter muscles and 0.9% normal saline (0.3ml) into L’t masseter muscles. Group II-injection of 5.0u BTXA(0.3ml) into R’t masseter muscles and 0.9% normal saline (0.3ml) into L’t masseter muscles. Group III-injection of 2.5u BTXA(0.3ml) into R’t masseter muscles and 0.9% normal saline (0.3ml) into L’t masseter muscles. Group IV- injection of 0.9% normal saline (0.3ml) into R’t masseter and L’t masseter muscles.Thereafter , rats were constantly feeded within 2 hours daily, and EMG signals were recorded for 12 weeks. After 12 weeks of EMG recording, the rats were perfused and sacrificed. The EMG data were analyzed for statistic calculation, and the weights of masseter muscles were measured. The results showed that :(1)In general, masseter muscle activity variables decreased over 90% during the first week after injection of BTXA on the experimental side of Group I, II, III. (2)In Group III, muscle activity variables gradually recovered from 3rd~4th week after injection ; in Group I and Group II, the muscle activity recovered from 4th~6th week after injection. (3) On the 12th week, in Group I and Group II, the muscle RMS amplitude recovered to 28%~33% ; in Group III , the RMS amplitude recovered to 55 % compared to the preinjection activity levels.(4) In Group IV, there was no significant change of muscle activity before and after normal saline injection. (1)With the injection of BTXA, the activity of masseter muscle and the muscle weight were significantly decreased.(2)With the BTXA doses increasing, the greater muscle activity depression was noticed. Compared with Group III, there were greater decreases of muscle activity in Group I and II.(3)Among all the three experimental groups(GroupI, II, and III), muscle activity was remained depressed and never returned to preinjection levels even after 12 weeks investigation period starting from BTXA injection.

並列關鍵字

masseter muscle ； Botulinum toxin A ； EMG

參考文獻

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