辣椒素引起大鼠聲門關閉的神經調控機制

Abstract

文獻上報導以辣椒素刺激肺C纖維，會引起呼吸暫停、血壓下降、心跳變慢三合一反射性反應，是一種防禦性保護機制，可以減緩有害物質的入侵及傷害。若是可以將刺激性物質阻擋使之不能進入，應該可以更加有效保護我們的呼吸系統，避免更多的侵害。喉部的聲門是控制呼吸道打開與關閉的閘門，也就是呼吸氣流必經的通路，控制喉部聲門外展 (開啟) 與內收 (關閉) 的神經是喉返神經。本研究目的在探討肺C纖維興奮對大鼠喉返神經呼吸活動的影響，藉以探討聲門是否會因為肺C纖維興奮而緊閉。 本研究選用Wistar品系雄性大鼠，利用辣椒素興奮肺C纖維，分為四部分實驗進行。第一，從右頸靜脈注入辣椒素以興奮肺C纖維，觀察甲杓肌活性之反應、聲門下壓力以及聲門外展與內收的變化，以研究聲門是否真的關閉；第二，投予辣椒素興奮肺C纖維，觀察喉返神經呼吸活動的反應；第三，同樣興奮肺C纖維，觀察控制聲門打開的喉返神經外展支吸氣活動以及控制聲門內收支的呼氣活動之變化；第四，研究單一喉返神經呼吸神經元對肺C纖維興奮的反應以解釋喉返神經的反應機制。 研究所得結果顯示，辣椒素由右頸靜脈注射進入右心房，以興奮肺C纖維時，會引起呼吸暫停、血壓降低及心跳變慢反應，在呼吸暫停與恢復期間，甲杓肌活動 (即TA EMG) 增強，導致聲帶內收、聲門緊緊關閉，使呼氣氣流無法順利通過聲門，引起聲門下壓力大大增加，以數位相機透過立體解剖顯微鏡，可以同步攝影，拍下實驗過程中，聲門的確在辣椒素的作用下緊緊關閉；整條喉返神經呼氣與吸氣活動都顯著增強，呼氣活動增強可能會促使聲門關閉，有利於保護肺與呼吸道免於再受到刺激性氣體的刺激，可是，在膈神經活動逐漸恢復時，整條喉返神經吸氣活動增強，使聲門展開，卻可能使肺與呼吸道更容易受到有害氣體的侵襲；這種不合理的反應，從同時記錄外展支與內收支對辣椒素的反應得到解釋，其實外展支的吸氣活動是降低的，但是由於喉返神經內收支在辣椒素作用下，非常興奮而轉變成為連續性活動，使得整條喉返神經呼吸活動外觀宛如增強似的，在內收支活動增強下，使內收支所支配的甲杓肌活動增強，於是聲門關閉。 到底辣椒素刺激後，喉返神經的反應機制是甚麼？這個部分是藉由分離並記錄喉返神經單根纖維，來解答整條喉返神經對辣椒素作用所引起的反應機制，這個實驗可以幫助我們更清楚了解當肺C纖維受到刺激時，喉返神經到底產生什麼樣的反應機制來因應並調控聲門的開啟與關閉。這個部分的實驗結果顯示，興奮肺C纖維會抑制吸氣神經纖維 (I) 和呼與吸神經纖維 (E-I)，卻會增強呼氣神經纖維 (E) 以及激活靜態神經纖維 (S) 參與放電反應，不僅如此，有些呼氣神經纖維還會提前於吸氣時活動起來，有些則轉變為連續性放電，這些吸氣相關神經細胞放電率受到抑制，呼氣神經細胞受到興奮、並提前活動，可充分說明喉返神經外展支與內收支的反應機制，以作為聲門因應辣椒素作用而關閉起來的神經生理學依據。 總之，以辣椒素興奮肺的C纖維，會引起反射性反應，導致聲門緊閉、呼吸暫停、降壓以及抑心作用，以降低有害氣體對呼吸道及肺更進一的傷害，這些反應對呼吸道與肺可能具有防禦性保護作用。

Pulmonary C-fiber (PCF) activation by capsaicin is known to produce apnea, hypotension and bradycardia. This triad response of cardiopulmonary chemoreflex has been thought as a combined protective mechanism for the airways and lungs to prevent further insults. However, a defensive protection may be more efficient if the irritant can be kept from entering the respiratory system. The movement of the vocal cords, which is innervated and controlled by the recurrent laryngeal nerves (RLN), may be a good candidate for this defensive mechanism. The purpose of the present study was designed to investigate whether the vocal cords were closed in response to capsaicin administration and to study the neural regulation by recording respiratory-related activities of the RLN when the PCF was activated by capsaicin. Wistar strain of rat was used in the present study. PCF was activated by capsaicin administration via the right jugular vein. Four experiments were performed. The first experiment was to record electromyogram (EMG) activity of the thyroarytenoid muscle (TA), the main adductor, and the subglottal pressure (SGP), and also to observe the vocal cord movement in response to capsaicin administration. The second study was to trace the response of the respiratory-related activity of the RLN to capsaicin administration. In the third experiment, activities of the abducent and adducent branches of the RLN, innervating the abducent and adduct muscles, respectively, were examined of their responses to capsaicin administration. The final experiment was designed to explain the mechanism of the RLN response to capsaicin administration by recording single fiber activities of the RLN. The results demonstrated that PCF activation by capsaicin administration could produce the triad cardiopulmonary chemoreflex and a concomitant increase in TA EMG throughout the apnea and a period of recovery from the apnea. This increase in TA EMG adducted the vocal cords to close the glottis, which in turn to lead to a large increase in SGP. In response to capsaicin delivery to the right jugular vein, the RLN activity was immediately enhanced during the apneic period and also the recovery from the apnea. The enhancement of RLN activity during expiration after recovery from apnea might give a good evidence for the protective role due to the adduction of the vocal cords to close the glottis. However, the enhanced RLN activity during inspiration after recovery might be even worse in term of the protective role. The contradictory phenomenon could be explained by the observation of thyroarytenoid branch of the recurrent laryngeal nerve (TA RLN), showing changing its discharge earlier to commence from the early expiratory stage to inspiration so that a continuous activity had occurred. In fact, the activation of the abducent branch of the recurrent laryngeal nerve (Abd RLN) activity was reduced by capsaicin treatment. The increase in activity of the TA or adducent branch of the RLN and its advanced onset to commence earlier during TI might give an explanation why the whole RLN activity during inspiration after recovery from apnea was still higher than control. Using single fiber recording technique, we found 4 types of recurrent laryngeal motoneurons, which were the inspiratory (I), expiratory-inspiratory (E-I), expiratory (E), and silent (S) types. In response to capsaicin administration, activities of E-I and I were inhibited while E and S were excited. Moreover, some E motoneurons were advanced their onset time to commence earlier during inspiratory period and some E neurons were continuously discharged throughout the period of inspiration and expiration with capsaicin administration. These responsive patterns of laryngeal motoneurons might underlie the notion that capsaicin administration could produce glottal constriction through the excitation on the TA branch of the RLN. In summary, data obtained in the present study demonstrated that an increase in adducent (TA) branch of the RLN activity caused by capsaicin administration might result in augmentation of TA EMG to drive the vocal cords to close the glottis tightly. The combination of glottal closure with apnea, hypotension, and bradycardia might provide a highly effective protective mechanism for the airways and lungs to prevent further insults by irritant.