Shah A A, Byrne M F, Cullen L, Walsh T, Fitzgerald D J, Murray F E
Royal College of Surgeons in Ireland, Ireland.
Prostaglandins Leukot Essent Fatty Acids. 2003 Jan;68(1):1-8. doi: 10.1016/s0952-3278(02)00228-4.
Cyclooxygenase-1 is the primary isoform responsible for the production of cytoprotective prostaglandins (PGE(2) and PGI(2)) in the stomach. In contrast COX-2 is induced at the sites of inflammation. Using Helicobacter pylori infection as a model of inflammation, this study was designed to evaluate the effects of H. pylori infection on prostanoid synthesis and expression of COX-2 in human gastric mucosa. Prostaglandin (PGE(2)) and prostacyclin (PGI(2)) synthesis in gastric biopsies obtained from 21 patients undergoing diagnostic endoscopy, were determined. H. pylori was detected by CLO test, histology and culture. Biopsy samples were incubated either with NS-398, selective COX-2 inhibitor or aspirin. Samples were also treated with endotoxin (LPS) in order to induce COX-2 expression. Tissue was also analysed for COX-2 expression in vivo by immunohistochemistry. In 15 out of 21 patients, H. pylori was detected by at least two of the three methods. Higher levels of PGE(2) and PGI(2) were seen in patients infected with H. pylori (191+/-30 and 245+/-88ng/mg protein, respectively) compared with non-infected patients (77+/-17 and 120+/-36ng/mg protein, respectively). There was significant inhibition of PGE(2) and PGI(2) with aspirin in both H. pylori infected (28+/-6.6 and 53+/-43ng/mg, respectively) and in non-infected patients (16+/-7 and 12.5+/-3.5ng/mg protein, respectively). However, NS-398 and LPS did not alter prostaglandin function significantly. Immunohistochemistry in all patients irrespective of Hp status demonstrated expression of COX-2.Lower concentration of constitutive expression of COX-2 was detected in human gastric mucosa by immunohistochemistry, however, H. pylori infection failed to induce COX-2 protein. In addition, increased prostaglandin synthesis in Hp-infected patients appears to be COX-1 mediated rather than COX-2. Furthermore, failure of endotoxaemia-treated sample to produce more PGE(2) in the face of enhanced COX-2 expression in gastric mucosa further suggests that increased prostanoids in human gastric stomach are COX-1 mediated.
环氧化酶-1是胃中负责产生细胞保护性前列腺素（PGE₂和PGI₂）的主要亚型。相比之下，COX-2在炎症部位被诱导产生。以幽门螺杆菌感染作为炎症模型，本研究旨在评估幽门螺杆菌感染对人胃黏膜中前列腺素合成及COX-2表达的影响。测定了从21例接受诊断性内镜检查的患者获取的胃活检组织中前列腺素（PGE₂）和前列环素（PGI₂）的合成。通过CLO试验、组织学和培养检测幽门螺杆菌。活检样本分别与NS-398（选择性COX-2抑制剂）或阿司匹林一起孵育。样本还用内毒素（LPS）处理以诱导COX-2表达。还通过免疫组织化学分析组织中COX-2在体内的表达。21例患者中有15例通过三种方法中的至少两种检测到幽门螺杆菌。与未感染患者（分别为77±17和120±36ng/mg蛋白质）相比，感染幽门螺杆菌的患者中PGE₂和PGI₂水平更高（分别为191±30和245±88ng/mg蛋白质）。阿司匹林对感染幽门螺杆菌的患者（分别为28±6.6和53±43ng/mg）和未感染患者（分别为16±7和12.5±3.5ng/mg蛋白质）的PGE₂和PGI₂均有显著抑制作用。然而，NS-398和LPS并未显著改变前列腺素功能。无论幽门螺杆菌状态如何，所有患者的免疫组织化学均显示COX-2表达。通过免疫组织化学在人胃黏膜中检测到较低浓度的COX-2组成性表达，然而，幽门螺杆菌感染未能诱导COX-2蛋白产生。此外，幽门螺杆菌感染患者中前列腺素合成增加似乎是由COX-1介导而非COX-2。此外，面对胃黏膜中COX-2表达增强，内毒素血症处理的样本未能产生更多PGE₂，这进一步表明人胃中前列腺素增加是由COX-1介导的。
