幽門桿菌的感染與許多胃部相關疾病有很大相關性。除了細菌與環境因子外，宿主體內所發生的免疫反應，對於不同的臨床症狀亦佔有很重要的角色，然而在東西方國家對於IL-1多型性與不同病理變化間相關性的研究並不一致。Matrix metalloproteinases (MMPs) 是一群能分解大多數細胞外基質的蛋白酶，參予了發炎反應與腫瘤的生長與轉移，幽門桿菌的感染亦會誘發許多的MMPs的釋放，並且受到IL-1等細胞激素的調控。本論文第一部分是探討不同的胃部相關疾病與IL-1多型性之間的相關性。由成大醫院收集394位病人的血液與組織檢體，其中78位無幽門桿菌感染，316位有幽門桿菌感染，SSOP用於IL-1B基因啟動子-31與-511單一核甘酸多型性的分型，而IL-1RN基因intron 2中的penta-allelic 86-bp tandem repeat是採用電泳方式分析，病理變化指數的判讀是依據update Sydney System。完成分析後發現，IL-1B基因啟動子-31與-511多型性存在連鎖不平衡的關係，其分布的頻率與幽門桿菌的感染率及不同的診斷間皆無顯著性差異 (p < 0.05)。分析感染幽門桿菌並診斷是十二指腸潰瘍與胃潰瘍的病人，其-31C或-511T對偶基因相較於-31T或-511C並無任何病理變化的差異性，只有在診斷是非潰瘍性胃炎的病人中，帶有-31CC或-511TT者有增加嚴重慢性發炎的程度，尤其是在cardia更為嚴重 (p > 0.05)。這些感染幽門桿菌的病人，pepsinogen Ⅰ/Ⅱ比例可下降達30.3%之多。在我們的檢體中IL-1RN幾乎都是屬於1/1同型合子，並且也與幽門桿菌的感染率無關。基於以上的結果，我們發現在台灣人口中IL-1啟動子多型性僅促進了在感染幽門桿菌的非潰瘍性胃炎病人cardia處的慢性發炎程度。
論文第二部分主要是探討MMP-3、-7、-9，TIMP-1及-2在幽門桿菌感染後診斷為不同胃相關疾病病人中的表現與分布情形。利用免疫化學組織染色後判讀所有MMPs與TIMPs的表現與分布，一共有32位十二指腸潰瘍病人，32位非潰瘍性胃炎病人及27位胃潰瘍病人。經過統計分析，TIMP-1在十二指腸潰瘍的表現高過其他疾病的表現，特別在antrum達到統計上的差異；MMP-3的表現在非潰瘍性胃炎病人兩者的表淺上皮細胞層部位有顯著增加，MMP-9的表現在胃潰瘍病人中不論antrum與body的表淺上皮細胞層部位與固有層皆有明顯表現。胃潰瘍病人的潰瘍處的表淺上皮細胞層比非潰瘍處皆有較高的免疫反應，並有顯著的統計差異 (p < 0.001)。MMP-3、-7及-9 在杯狀細胞中也呈現較強的陽性反應。我們也利用幽門桿菌與其cagA-, vacA- and babA2-突變株感染人類胃上皮細胞AGS細胞株，結果發現不論是MMP3的mRNA程度及活性皆不會受到影響。基於以上MMPs與TIMPs的研究，我們得知MMPs或TIMPs在不同疾病間存在不同趨勢的表現，並且在潰瘍處更是有顯著的表現。

Helicobacter pylori infection is associated with wide spectrum of gastric diseases. Besides the bacterial and environmental factors, immune reactions of the infected host also play important roles to the different clinical outcomes. However, the association between the frequency of IL-1 polymorphisms and many different pathological events is controversy in western and eastern countries. Matrix metalloproteinases (MMPs) are a family of enzymes that degrade most extracellular matrix and participate with the roles in inflammatory processes, tumor growth and metastasis. Several MMPs can be induced during H. pylori infection and regulated by cytokines such as IL-1. The aim of first part in this study was to understand the relationship among different gastric associated diseases to IL-1 polymorphisms. Total 394 patients including 78 with and 316 without H. pylori infection were studied. Blood samples and tissue biopsies were collected from NCKU hospital. The polymorphisms of IL-1B promoter at -31 and -511 were checked by SSOP, and penta-allelic 86-bp tandem repeat of IL-1RN was checked by electrophoresis. Histopathology was reviewed by the update Sydney System. Both of the polymorphisms in near-complete linkage disequilibrium was not related to the prevalence rate of H. pylori infection and different results of diagnosis (p > 0.05). To analyze the association between H. pylori-related histology and IL-1 polymorphisms, -31C or -511T allele does’t have significant difference of histology compared to -31T or -511C in duodenal and gastric ulcer. Only non-ulcer dyspepsia patients carried with -31CC or -511TT increased the possibility of severe chronic inflammatory especially in cardia (p > 0.05). The pepsinogen Ⅰ/Ⅱ ratio significantly decreased 30.3% in H. pylori infected patients. IL-1RN genotypes were almost IL-1RN 1/1 allele and not related to H. pylori infection. Base on above data, we demonstrate that IL-1 promoter polymorphisms in our population only promote cardia chronic inflammatory in NUD patients infected with H. pylori.
The aim of the second part was to demonstrate the expression and location of MMP-3, -7, -9, TIMP-1 and -2 among different gastric associated diseases after H. pylori infection. The expression and location of MMPs and TIMPs were detected with immunohistochemistry including 32 DU, 32 NUD and 27 GU patients. DU was the highest TIMP-1 expression than others especially at antrum. MMP-3 expression increased on superficial epithelium of both antrum and body in NUD. MMP-9 dominantly expressed on superficial epithelium and lamina propia of both antrum and body in GU. All of the immunoreactions on superficial epithelium were significantly higher at ulcer than non-ulcer part of GU (p < 0.001). MMP-3, -7 and -9 were shown more intensity at goblet cells. We also infected AGS cells with H. pylori and isogenic mutants, cagA-, vacA- and babA2-. The results showed no effect the MMP-3 expression either in mRNA level or activity. Base on the study of MMPs and TIMPs, we demonstrate that MMPs or TIMPs have different expression trends among three diseases, and highly express at ulcer part.

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