- 學位論文
迷走神經在迷走-舌下神經雜接以及膽管結紮引發阻塞性黃疸中所擔任的角色與神經重塑之探討
The role and plasticity of vagus nerve in vagal-hypoglossal nerve coaptation and BDL-induced obstructive jaundice
摘要
迷走神經是具備四種不同功能成份（一般內臟傳出與傳入、特殊內臟傳出與傳入）的周邊神經，可支配胸腔及腹腔內臟的平滑肌與腺體並回傳該內臟的感覺訊息，亦可支配咽及喉部由咽弓衍生的骨骼肌並回傳喉及會厭處味蕾的味覺。因此迷走神經成為神經雜接以探討不同功能神經重塑作用的極佳材料；迷走-迷走感覺與運動神經迴路也成為探討在阻塞性黃疸傷害下，支配肝臟的一氧化氮性神經迴路所扮演的調控角色。本論文的第一部分，揭示在迷走-舌下神經雜接後，於縫合處展現的異質接合神經之退化、再生與重塑過程，有異於一般性同質神經的受傷與恢復，此乃因為雜接所新建立的神經徑路以及新取得的神經重支配標的器官，改變了一般性神經再生所賴以運作的環境之故。本論文的第二部分，揭示當迷走神經遭遇其支配器官肝臟受阻塞性黃疸傷害時，會全面激活小結神經節、孤立徑核與迷走神經背側運動核相關迷走神經迴路，尤其是上調一氧化氮性神經元內NADPH-d/nNOS的活性表現，有助於一氧化氮的生成激增。因此可提升神經張力以促使膽囊將過多鬱積的膽汁排空，但亦造成微膽管鬆弛而加重膽汁滯留病變。此外，nNOS活性上升更可扮演保護性角色，促進肝竇狀隙擴張，以補償因肝竇狀隙內皮細胞失能所導致的一氧化氮量減少，因而緩和因肝內血流阻力上升而導致的門脈性高血壓。
並列摘要
The vagus nerve is a peripheral nerve that has four different types of functional components, i.e. general visceral afferents and efferents, special visceral afferents and efferents, and can innervate smooth muscles and glands in the thorax and abdomens while carries back visceral information of target organs concurrently, also the nerve can send back tastes from the larynx and epiglottis and innervate skeletal muscles derived from the pharyngeal arches of pharynx and larynx. Accordingly, the vagus nerve becomes one of the popular research materials of nerve plasticity and how its sensory and motor fibers in vago-vagal neural circuit play a role in regulation of hepatic nitroxidergic neural circuit under obstructive jaundice will be examined. The first part of this research will show how different the process of degeneration, regeneration and remodeling of hetero-connected nerve at the suture site after vagal-hypoglossal coaptation from that of injury and recovery of common connatural nerve connection, for the newly established neural pathways and reinnervation of new targets after nerve heteroconnection have changed the original neural environment when they regenerated. The second part of this research will show activation of nodose ganglion, nucleus of solitary tract, and dorsal motor vagal nucleus related vagal circuit globally when the vagus nerve encountered with injuries of obstructive jaundice of liver. Especially the upregulation of NADPH-d/nNOS reactivity in the liver-innervated vagal neurons may elevate NO synthesis significantly, which can raise up the parasympathetic tone that benefit to the gallbladder emptying excess stagnant bile but also worsen the pathogenesis of cholestasis by impairing canalicular contraction. Besides, the increase of nNOS reactivity plays a protective role in compensating for the deficient eNOS-mediated NO of dysfunctional sinusoidal endothelial cells by promoting relaxation of sinusoidal walls, thus reduces resistance to intrahepatic blood flow and alleviates the liver from subsequent development of portal hypertension.