肉毒桿菌神經毒素對芥末油引發發炎反應的抑制效果

Inhibitory Effect of Botulinum Neurotoxin on Mustard oil-induced Inflammation

楊正昌(Jan-Chang Yang) ； 鄧乃嘉(Nai-Chia Teng) ； 李勝揚(Sheng-Yang Lee) ； 蔡志孟(Chih-Mong Tsai)

《中華牙醫學雜誌（中文版）》 1卷3期 (2005/09) Pp. 165-173

https://doi.org/10.7106/CJD.200509.0165

摘要

當週邊感覺神經C-纖維受到傷害性刺激而興奮時，具備強烈的血管擴張效力的neurokinins會由原先存放的末梢小泡(vesicle)中釋放出來，作用到周圍組織中會引起發炎反應；這種現象顯示週邊感覺神經C-纖維是造成發炎反應的重要元素之一，而neurokinins則是引起發炎的神經性化學中介物質。末稍小泡釋放內含物質需要啟動vesicle docking system，幾乎所有的真核細胞生物控制細胞小泡釋放之機制十分雷同，肉毒桿菌神經毒素(botulinum neurotoxin)可以破壞運動神經的vesicle docking system，阻止乙醯膽鹼(acetylcholine)自運動神經纖維末梢的小泡釋放出來，造成肌肉麻痺。我們大膽假設肉毒桿菌神經毒素也可以阻止neurokinins自C-纖維末梢釋放，進而抑制神經性發炎反應的產生。本研究希望藉由動物實驗來探討：(1)肉毒桿菌神經毒素預先注射對芥末油注射大白鼠後腳掌引起的發炎反應（包括血漿外滲以及組織腫脹）的抑制效果與作用所需的時間；(2)比較肉毒桿菌神經毒素、局部麻醉劑Lidocaine及neurokinins NK-1型受器拮抗劑L-733060對芥末油引發的發炎反應的抑制效果，並依不同藥劑之特殊作用部位推論肉毒桿菌神經毒素抑制發炎反應的作用機制。實驗結果顯示：(1)芥末油注射於預先注射生理食鹽水之後腳掌引起嚴重的腫脹及血漿外滲；(2)預先注射5U之BOTOX、Lidocaine或L-733060可有效減低此一發炎反應；(3)5U BOTOX在注射7天後開始發揮效果，此一效果維持至少十天。上述結果顯示BOTOX具有抑制芥末油注射引起的神經性發炎之效果！

關鍵字

肉毒桿菌神經毒素 ； 芥末油 ； 神經性發炎反應 ； 腫脹 ； 血漿外滲

並列摘要

Primary afferent C-fibers have been regarded as a critical element for the inflammatory reaction and neurokinins stored in the vesicles at the peripheral endings of C-fibers as important inflammatory mediators. Upon excitation of the C-fibers, neurokinins are released from containing vesicles into surrounding tissues, resulting in vasodilatation. Botulinum neurotoxin is known to paralyze muscles by preventing the release of acetylcholine from the vesicles at the peripheral endings of motoneurons. The control mechanisms for vesicular release appear to be extremely similar among almost all eukaryotic organisms, from yeasts, a lower level unicellular organism, to brain cells of advanced primates. Therefore, this study aimed to test the inhibitory effect of botulinum neurotoxin on inflammation and to compare the inhibitory effects with those of lidocaine (a topical anesthetic) and L-733060 (an antagonist for the neurokinin NK-1 type receptor). The results showed that a pre-injection of 5U BOTOX, 2% lidocaine, or L-733060 (1mg/kg) all effectively reduced the evoked inflammation and the botulinum neurotoxin commenced to act 7 days after the pre-injection with a duration of at least 10 days. This study suggests that botulinum neurotoxin has an inhibitory effect on neurogenic inflammation.

並列關鍵字

botulinum neurotoxin ； mustard oil ； neurogenic inflammation ； swelling ； Evans blue extavasation