評估腸胃道系統的功能性疾病患者之胃黏膜神經支配結構上的改變

Structural assessments of functional disease in the gastrointestinal system by mucosa innervation of the stomach

黃睦展(Mu-Jhan Huang)

指導教授 ： 謝松蒼

國立臺灣大學/醫學院/解剖學暨細胞生物學研究所/碩士(2016年)

https://doi.org/10.6342/NTU201602476

摘要

傳統上，功能性胃腸障礙 (functional gastrointestinal disorders) 的評估都只能透過症狀的描述，但是缺少客觀且可量化的分析方式來檢驗是否有結構上的改變。功能性消化不良症候群 (functional dyspepsia) 是其中一種常見的功能性胃腸障礙，這一症候群的定義是：患者在上腸胃道出現消化不良的症狀，但在內視鏡檢查下腸胃道並無異常，且也沒有其他代謝性及系統性的疾病可以用來解釋。目前臨床上並沒有病理生理學的診斷方式，只能依據羅馬診斷標準 (Rome criteria)來進行診斷。從病理生理學的角度上來看，功能性消化不良症候群的病因是十分複雜且異質性相當高的一種疾病，而我們的假說是：功能性消化不良症候群的產生或許是由於胃黏膜上的神經支配出現了結構上的改變而導致。所以，我們建立了一套系統來檢視並定量胃黏膜上的神經支配，利用免疫化學染色來染出胃黏膜上的神經，再透過體視學的方法來定量胃黏膜上的胃黏膜神經纖維密度 (mucosal nerve fiber density) ，除此之外，我們也嘗試建立另一套系統來替代體視學的定量方法。結果顯示，與對照組相比，胃黏膜神經纖維密度在功能性消化不良症候群患者的胃竇 (antrum) 、胃體 (body) 及胃底 (fundus) 皆有顯著性的下降 (p< 0.01) ；另一方面，比較兩種定量系統所得到的定量結果，不論是在控制組抑或是功能性消化不良症候群患者組皆有顯著的相關性 (r2= 0.8194, p= 0.0006; r2= 0.8184, p= 0.0006) 。綜上所述，透過所建立的胃黏膜神經纖維密度定量系統，我們發現在功能性消化不良症候群患者的胃黏膜神經纖維密度相比於控制組有顯著性的下降；另外，我們所建立的定量系統提供了一個新的平台來檢視功能性胃腸障礙患者的胃黏膜神經結構改變，也提供了一種新的方法來探討功能性胃腸障礙的病因。

關鍵字

胃黏膜 ； 黏膜神經纖維密度 ； 功能性胃腸障礙 ； 功能性消化不良症候群 ； 體視學

並列摘要

Traditionally, the assessments of functional gastrointestinal (GI) disorders depended on symptom description and lacked objective and quantitative analysis for examining structural alterations in these disorders. Functional dyspepsia (FD), one of these functional GI disorders, is defined as the presence of chronic or recurrent dyspepsia symptom localized in the upper abdomen without any organic, systemic or metabolic disease. Clinically, FD does not have well-established pathophysiology and could only be diagnosed by the updated Rome criteria. However, the pathophysiology of FD is complex, heterogeneous, and hard to completely elucidate. We hypothesized that the pathophysiology of FD could be related to the structural changes in the innervation of gastric mucosa leading to sensory or motor abnormalities. Thus, we set up a system to assess the innervation in the mucosa of stomach. We used the combination of well-established immunohistochemistry technique to obtain the image of mucosal nerves and stereological quantitative evaluation to acquire the mucosal nerve fiber density (MNFD) of three different gastric regions. We also tried to set up different quantitative methods for substituting the stereological method, i.e. the grid-counting method. Comparing the outcomes of control and FD patients between two different methods, they have a significant correlation (r2= 0.8194, p= 0.0006; r2= 0.8184, p= 0.0006). Furthermore, compared with control subjects, the MNFDs at the antrum, body, and fundus of stomach are all significantly decreased (p< 0.01) in FD patients. In conclusion, we have set up a system to quantify gastric mucosa innervation which provides a new approach to examine the structural alterations of functional GI disorders.

並列關鍵字

Gastric mucosa ； Mucosal nerve fiber density ； Functional dyspepsia ； Stereology ； Grid-counting

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