高位頸部脊髓損傷常會造成呼吸型態的改變，也可能會改變肺迷走傳入神經
的活性。肺C 纖維是肺部主要感覺化學刺激的傳入神經纖維。而辣椒素能刺激肺
C 纖維產生肺化學反射，例如：呼吸暫停、血壓降低與心跳變慢。先前研究指出在
切除單側頸部第二節脊髓後一天，辣椒素無法誘發大鼠產生肺化學反射。本論文
要探討在脊髓損傷後的慢性期，以辣椒素刺激肺C 纖維產生的肺化學反射是否恢
復與肺C 纖維的背景活性對於呼吸型態的影響。成年雄性Sprague-Dawley 大鼠會
接受切除單側頸部第二節脊髓或偽手術(以偽手術大鼠為控制組)，所有大鼠皆在麻
醉後自發性呼吸狀態下測量呼吸、心跳及血壓，手術後兩週或八週會以頸靜脈注
射辣椒素誘發肺化學反射。研究結果顯示手術後兩週與八週大鼠皆能產生肺化學
反射，不過完全切除單側頸部第二節脊髓的損傷組大鼠的呼吸暫停都會比控制組
弱。將完全與不完全切除單側頸部第二節脊髓手術後八週大鼠的呼吸型態與肺化
學反射以線性回歸統計發現損傷程度越輕，呼吸型態與肺化學反射會恢復得越接
近控制組。以辣椒素包住迷走神經處理阻斷肺C 纖維來探討肺C 纖維背景活性的
功能。結果顯示以辣椒素包住迷走神經能大幅度減弱辣椒素誘發的肺化學反射，
但是阻斷肺C 纖維並不影響完全切除單側頸部第二節脊髓或偽手術後八週大鼠的
呼吸型態。此論文的結論是慢性頸部脊髓損傷會減弱肺化學反射的呼吸反應，而
且會隨著損傷程度的減輕而恢復。不過慢性頸部脊髓損傷後呼吸型態改變並非肺C
纖維的背景活性所主導。肺化學反射在頸部脊髓損傷慢性期比起急性期有恢復顯
示病患在慢性期可能因為肺防禦性反射的恢復而減少肺部受到刺激而導致發炎的
可能性。

High cervical spinal cord injury usually changes the respiratory pattern, which may influence the pulmonary vagal afferent activity. Previous study revealed that pulmonary chemoreflex cannot be evoked following acute C2 hemisection (C2Hx). The first aim of this study is to examine whether capsaicin-induced chemoreflex can recover following chronic C2Hx. Adult male Sprague-Dawley rats received sham operation (i.e., control group) or C2Hx. Pulmonary chemoreflex were evoked by intra-jugular administration of capsaicin in 2 or 8 weeks post-surgery rats. Results showed that pulmonary chemoreflex can be evoked; however, the apneic period in complete C2Hx group was weaker than control group. Linear regression analysis of complete and incomplete C2Hx rats indicated that respiratory pattern and pulmonary chemoreflex recovered as the severity of spinal cord injury decreased. The second aim of the present study was to investigate whether background activity of lung C-fibers can influence the breathing pattern during the chronic injury phase by blocking lung C-fiber conduction using perivagal capsaicin treatment. Our data showed pulmonary chemoreflex was attenuated by perivagal capsaicin treatment; however the respiratory pattern was not changed after perivagal capsaicin treatment in control and complete C2Hx rats. We conclude that capsaicin-induced apnea was attenuated following chronic C2Hx; moreover, it recovers as the severity of spinal cord injury decrease. Nevertheless, respiratory pattern remains unchanged after blocking lung C-fibers. Recovery of pulmonary chemoreflex reveals that the occurrence of inflammation may decrease because the defensive reflex altered in the chronic phase.

論文審定書 .................................................................................................... i
中文摘要 ..................................................................................................... ii
英文摘要 ...................................................................................................... iii
目錄 .............................................................................................................. iv
圖次 ............................................................................................................. vii
表次 ............................................................................................................ viii
第一章 前言 ................................................................................................. 1
第一節 頸部脊髓損傷對呼吸的影響 ....................................................... 1
第二節 肺化學反射 ................................................................................... 4
第三節 目的 .......................................................................................... 7
第二章 材料方法 ......................................................................................... 9
第一節 實驗動物 ....................................................................................... 9
第二節 頸部第二節脊髓切除手術 ........................................................... 9
第三節 呼吸氣流與血壓測量 ................................................................... 9
第四節 辣椒素配製 ............................................................................ 10
第五節 以辣椒素包住迷走神經 ............................................................. 10
第六節 組織學 ......................................................................................... 10
第七節 實驗計畫表 ................................................................................. 11
第八節 數據分析與統計 ......................................................................... 12
第三章 結果 ............................................................................................... 14
第一節 肺化學反射於頸部脊髓損傷後的表現 ................................ 14
第二節 頸部脊髓損傷程度對於肺化學反射表現之影響 ................ 15
第三節 肺C 纖維背景活性對於頸部脊髓損傷動物呼吸型態的影響
.............................................................................................................. 16
第四章 討論 ............................................................................................... 18
第一節 方法討論 ..................................................................................... 18
第二節 慢性頸部脊髓損傷後肺化學反射的改變 ............................ 19
第三節 頸部脊髓損傷程度對呼吸型態與肺化學反射恢復的影響 22
第四節 迷走C 纖維背景活性對於慢性頸部脊髓損傷後呼吸型態的
影響 ...................................................................................................... 23
第五節 結論 ........................................................................................ 25
第五章 圖與說明 ....................................................................................... 26
第六章 表與說明 ....................................................................................... 43
第七章 參考文獻 ....................................................................................... 44
第八章 附錄 ............................................................................................... 53
第一節 補充數據 ..................................................................................... 53
辣椒素溶劑對於肺化學反射之影響 .............................................................. 53
辣椒素誘發肺化學反射的主要途徑 .............................................................. 58
肺C 纖維背景活性對於頸部脊髓損傷後兩週動物呼吸型態的影響 ...... 67
以辣椒素溶劑包住迷走神經對於肺C 纖維的影響 .............................. 73
以辣椒素包住迷走神經對於肺脹大反射的影響 .................................. 81
第二節 發表 ............................................................................................. 91

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