大鼠上呼吸道運動神經對於肺迷走傳入神經活化後反應之研究

Studies on Responses of the Upper Airway Motor Nerves to Activation of Pulmonary Vagal Afferents in the Rat

李昆澤(Kun-Ze Lee)

指導教授 ： 黃基礎

國立臺灣師範大學/理學院/生命科學研究所/博士(2006年)

摘要

上呼吸道包含鼻腔、咽部以及喉部，這段呼吸道的暢通主要由顏面、舌下、上喉和喉返神經的呼吸相關活性所控制。肺迷走傳入神經為肺部主要接受週邊刺激的傳入神經纖維，包含了肺C纖維、肺牽張慢速適應受器與快速適應受器。本論文的目的是探討大鼠肺迷走傳入神經興奮後對於上呼吸道運動神經的影響，為達此目的，本論文分成六個實驗，除第四個實驗外，其餘實驗所用的動物，都是麻痺並以人工呼吸機維持呼吸。第一實驗是研究大鼠舌下神經對於肺C纖維受到頸靜脈注射辣椒素後的反應，結果顯示肺C纖維興奮後會抑制舌下神經節律性的吸氣前與吸氣活性，並誘發短暫的連續性放電活性。舌下神經主要可以分為內支與外支舌下神經，這兩個分支分別支配舌頭的伸肌與縮肌，而肺C纖維興奮後所引起的反射作用，對於內支與外支舌下神經的影響是否相同並不清楚，因此，第二個實驗是同時紀錄內支與外支舌下神經，探討其對肺C纖維興奮後的反應，結果顯示肺C纖維興奮後會同時抑制內支與外支舌下神經的節律性活性，但只會誘發內支舌下神經產生明顯的連續性放電。為了進一步探究舌下神經對於肺C纖維興奮後的反應機制，論文的第三個實驗是利用單根神經分離技術，觀察舌下運動神經元的反應，結果顯示大鼠的舌下神經元包含了呼氣-吸氣神經元、吸氣神經元與靜止神經元，肺C纖維興奮後會抑制舌下神經的節律性活性主要是由於降低了呼氣-吸氣與吸氣神經元的放電率和放電起始時間，而舌下神經的連續性放電活性則可能是由於靜止神經元被辣椒素誘發放電所引起。論文的第四個實驗是要研究舌下神經所支配的舌肌所產生的力量，在肺C纖維興奮所引起的反射是否降低，為量測舌肌收縮所引發的力量，動物在自動呼吸情況下，短暫堵住呼吸道以誘發舌肌力量，發現堵塞呼吸道所誘發的舌肌前伸與後縮力量會增強，這種增強作用會被肺C纖維興奮所抑制，這些結果顯示肺C纖維受刺激後所引起的反射作用，會促使舌下神經活動與舌肌誘發力量降低，可能會不利於上呼吸道的暢通。
活化其他種類的肺迷走傳入神經對於上呼吸道運動神經可能會引起不同的效應，本論文的第五個實驗是研究上呼吸道運動神經(顏面、舌下、上喉與喉返神經)對於肺牽張慢速適應受器與快速適應受器活性改變所引起的反射性反應，方法是增加呼氣末正壓來改變上述兩類接受器的活性，將人工呼吸機的呼氣口接一小管，將管口插入水平面下以增加動物的呼氣末正壓，發現中等程度呼氣末正壓所引起的反射作用，會抑制上呼吸道運動神經與膈神經的吸氣節律，但卻不影響這些運動神經的吸氣前活動，這種現象為稱分開反應，換言之，上呼吸道運動神經在膈神經靜止不活動時仍保有節律性的放電，進一步記錄各運動神經的單根神經元活動，發現分開反應主要是由於中等程度呼氣末正壓會促進呼氣-吸氣神經元在呼氣時的活動，但卻抑制其在吸氣時的活動，可能是由於中等程度呼氣末正壓所引起這種不同的反射作用，才引起了分開反應，迴歸分析的結果顯示低到中等程度呼氣末正壓改變所引起的反射作對於呼氣-吸氣神經元在吸氣前(也就是呼氣)時期的放電率成線性增強，卻不影響其在吸氣時的放電率，暗示上呼吸道運動神經元在呼氣與吸氣時期，可能接受不同的調控作用。本論文最後一個實驗是探討甘胺酸抑制作用是否會調控上呼吸道的吸氣前活動，以證實上述所謂上呼吸道運動神經元接受不同調控的推論，實驗是以甘胺酸受器拮抗劑(strychnine)阻斷甘胺酸的傳導作用，結果顯示阻斷甘胺酸受器的作用後，不但使舌下神經在正常呼吸週期的吸氣前活動消失，且會抑制持續肺脹大所引起的吸氣前活性增強，顯示甘胺酸傳導作用可能與上呼吸道運動神經的吸氣前活動有關。綜合本論文研究所得的結果，顯示幾個結論是：(1)肺C纖維興奮後引起的反射作用可能經由抑制舌下神經與舌肌活性來影響上呼吸道的暢通；(2)藉由改變呼氣末正壓來調節肺牽張慢速適應受器與快速適應受器的活性會導致上呼吸道運動神經與膈神經的呼吸節律分離，此結果可能是增加呼氣末壓力會促進上呼吸道吸氣前活性並抑制吸氣活性所導致，暗示上呼吸道運動神經與膈神經的呼吸節律可能受到不同的調控，且上呼吸道運動神經在吸氣前與吸氣時的活動可能也受到不同的調節；(3)甘胺酸的抑制作用可能參與調節上呼吸道運動神經的吸氣前活

關鍵字

上呼吸道 ； 迷走傳入神經 ； 肺 ； 大鼠

並列摘要

The upper airway (UAW) is composed of the nasal cavity, pharynx and larynx. The patency of the UAW is primarily controlled by the respiratory-related activity of the UAW motor nerves, such as the facial, hypoglossal, superior laryngeal and recurrent laryngeal nerve. Pulmonary vagal afferents, including pulmonary vagal C-fiber (PCF) receptors, slowly adapting stretch receptors (SARs) and rapidly adapting receptors (RARs), are the main sensory afferents arising from the lungs and play an important role in regulating respiration. However, modulation of pulmonary vagal afferents on the UAW motor activity has not yet fully understood. Purpose of present dissertation was to investigate responses of the UAW motor nerves to pulmonary vagal afferent activation in the rat. At first, responses of the hypoglossal nerve to PCF receptor activation by intra-jugular capsaicin administration were examined in the anesthetized and artificially ventilated rats. The results showed that capsaicin-induced PCF receptor activation produced reflex inhibition on phasic (pre-inspiratory; Pre-I, and inspiratory; I) activity but excited tonic activity of the whole hypoglossal nerve. This raised a question whether decrease in the two branches, the medial hypoglossal branch (MHN) innervated the tongue protrudor muscles and lateral hypoglossal branch (LHN) supplied to the tongue retractor muscles was similar or dissimilar. To answer this question, the MHN and LHN were simultaneously recorded to examine their response to capsaicin treatment. The results showed that phasic activity of both hypoglossal branches was similarly reduced, while tonic activity was significantly evoked in the MHN versus LHN. To evaluate the motoneuronal activity underlying the hypoglossal discharge during PCF receptor activation, data from single fiber recording on these two hypoglossal branches revealed that decrease in phasic hypologlossal activity was mainly due to the decrease in discharge rate and a delay onset of the expiratory-inspiratory (EI) and inspiratory (I) hypoglossal motoneurons. However, tonic hypoglossal activity was resulted from the recruitment of silent hypoglossal motoneurons. Results from a further study showed that both protrusive and retractive tongue force development were reduced following intra-jugular capsaicin injection in spontaneously breathing rats. These results suggest that PCF receptor activation by capsaicin may have produced a disadvantage or even risk for the UAW patency. In contrast, activation of other pulmonary vagal afferents, such as SARs and RARs, may have produced distinct effects. Activation of SARs and RARs was achieved by changing positive end-expired pressure (PEEP). The results indicated that elevation of PEEP induced uncoupling of UAW phasic activity from the phrenic burst. This uncoupling was primarily due to a result of persistent firing of Pre-I of the UAW nerves and of the EI motoneurons during phrenic apnea caused by increasing PEEP. Data from the analysis by linear regression illustrated a differential influence of PEEP on EI motoneurons during Pre-I duration vs. I phase. Finally, blockade of glycinergic transmission by strychnine attenuated Pre-I activity of the hypoglossal nerve during control condition, and also during the advanced onset of the Pre-I activity caused by increase of PEEP and sustained lung inflation. In conclusion, the present results suggest that: (1) PCF receptor activation may produce a unfavorable modulation of the pharyngeal patency by the decrease in activity of the hypoglossal nerve and in tongue force development, (2) alteration of SARs and RARs activity by manipulating PEEP evokes an excitation on Pre-I but inhibition on I activity of the UAW motor nerves, and (3) glycinergic inhibition is probably critical for regulation of Pre-I activity of the UAW motor nerves.

並列關鍵字

upper airway ； vagal afferents ； lung ； rat

參考文獻

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