- 學位論文
A型肉毒桿菌神經毒素對電刺激引發的神經性發炎之抑制作用
Inhibitory Effects of Botulinum Neurotoxin Type A on Electrical Stimulation-Induced Neurogenic Inflammation
摘要
本實驗室之前的實驗顯示預先注射5單位A型肉毒桿菌神經毒素（botulinum neurotoxin type A; BoNT-A）可以抑制芥末油注射所引發的發炎反應，但肉毒桿菌神經毒素抑制發炎反應的機制在文獻中尚無解釋。本實驗將以電刺激坐骨神經在大白鼠後腳掌引發一純粹的神經性發炎，並以此實驗動物方法探討（1）BoNT-A對於神經性發炎的抑制作用；（2）比較不同的發炎抑制劑（例如：局部麻醉劑Lidocaine、鈣離子通道阻斷劑Omega-conotoxin GVIA、Neurokinin-1 receptor拮抗劑L-733060與BoNT-A）對電刺激引起的神經性發炎的抑制作用，以便進一步探討BoNT-A對發炎反應抑制作用的機轉。實驗結果顯示：（1）以坐骨神經電刺激可以在大白鼠後腳掌引發明顯的腫脹及血漿外滲；（2）BoNT-A、Lidocaine、Omega-conotoxin GVIA以及L-733060都能顯著減少（但不能完全抑制）電刺激引發的腫脹；（3）只有Lidocaine與Omega-conotoxin GVIA能有效減少血漿外滲，BoNT-A與L-733060則無此效果。上述結果顯示BoNT-A確實能有效降低部分神經性發炎反應，但BoNT-A是否也能抑制非神經性的發炎反應，則需進一步的實驗才能證實。
並列摘要
Our previous study has shown that pre-injections of 5U botulinum neurotoxin type A (BoNT-A) produces an anti-inflammatory effect on mustard oil injection-induced inflammation. However, the underlying mechanisms of this anti-inflammatory effect are currently unknown. Electrical stimulation of rat’s sciatic nerve was adopted in the present study to induce a pure neurogenic inflammation in rat’s hindpaw. The aims of this study were (1) to investigate the inhibitory effect of BoNT-A on the electrical-stimulation-induced neurogenic inflammation, and (2) to compare the anti-inflammatory effects of BoNT-A, lidocaine (a local anesthetic), omega-conotoxin GVIA (an N-type calcium channel blocker), or L-733060 (an NK-1 receptor antagonist) in order to extrapolate the possible underlying mechanisms of the anti-inflammatory effects of BoNT-A. The results showed that (1) electrical stimulation of sciatic nerve indeed induced significant swelling and plasma extravasation in rat’s hindpaw, (2) BoNT-A, lidocaine, omega-conotoxin GVIA or L-733060 pre-injection significantly reduced (but not completely abolished) the induced swelling, and(3) lidocaine and omega-conotoxin GVIA also significantly reduced the induced plasma extravasation, but BoNT-A and L-733060 did not have such effect. In conclusion, our results have provided direct evidence indicating a partial inhibitory effect of BoNT-A on neurogenic inflammation. However, whether BoNT-A also inhibits the non-neurogenic components of inflammation is unclears.