Mechanism for gastric carcinogenesis by H.pylori infection

我们研究了新生胸腺切除BALB/c小鼠幽门螺杆菌感染引起各种肿瘤病变的机制。出生后3天行胸腺切除术，术后2个月口服幽门螺杆菌感染，结果如下：1。当我们将幽门螺杆菌感染BALB/c小鼠时，持续感染的情况很少发生，而且我们几乎没有观察到胃粘膜炎症。相反，出生后3天去胸腺的BALB/c小鼠感染幽门螺杆菌后，所有小鼠均出现持续性感染，并伴有明显的胃黏膜炎症。感染后3个月，小鼠胃窦黏膜发生肠化生。在这些去胸腺的小鼠中，10%的小鼠在感染后6个月发生胃腺瘤。但感染1年后仍未见胃癌发生。在这些去胸腺的小鼠中，淋巴滤泡发育异常，感染2个月后，70%的小鼠发展为胃MALT淋巴瘤。在这些小鼠中，约30%的小鼠在感染1年后观察到类胃癌的形成。小鼠血清胃泌素浓度为1450 * 96 pg/ml，显著高于未感染小鼠（116 * 10 pg/ml）和未形成类癌的感染小鼠（765 * 56 pg/ml） （P < 0.01）。此外，在用一种特殊的胃泌素受体拮抗剂AG041R治疗的感染小鼠中，没有观察到类癌的形成。胃MALT淋巴瘤、胃腺瘤和胃类癌没有同时发生。7 .幽门螺杆菌数量和血清胃泌素水平排序为类癌>腺瘤> MALT淋巴瘤，胃酸分泌排序为MALT淋巴瘤>腺瘤>类癌。宿主的酸分泌能力、激素分泌能力和免疫反应等因素可能是决定各种疾病表型发生的重要因素。少

We examined mechanisms for development of various neoplastic lesions by H.pylori infection in neonatal thymectomized BALB/c mice. Thymectomy was performed 3 days after birth, and H.pylori was infected orally at 2 months after thymectomy, and following results were obtained :1. When we infected H.pylori to BALB/c mice, persistent infection did not occur so often, and moreover, we hardly observed mucosal inflammation of the stomach.2. In contrast, when H.pylori was infected to BALB/c mice thymectomized 3 days after birth, persistent infection developed in all the mice, which was associated with prominent inflammation of the gastric mucosa.3. In these mice, intestinal metaplasia developed in the antral mucosa at 3 months after the infection.4.In these thymectomized mice, 10% of them developed gastric adenoma at 6 months after the infection. However, gastric cancer could not be observed even 1 year after the infection.5. In these thymectomized mice, development of lympho-follicles was obse … More rved 2 months after the infection, and moreover, 70% of them developed gastric MALT lymphoma.6. In these mice, gastric carcinoid formation was observed at 1 year after the infection in about 30% of all the animals. Serum gastrin concentrations of these mice was 1450 * 96 pg/ml, whchi was significantly higher than that of non-infected mice (116 * 10 pg/ml) and that of the infected mice without carcinoid formation (765 * 56 pg/ ml) (P < 0.01). Moreover, in the infected mice who were treated with a specific gastrin receptor antagonist, AG041R, no carcinoid formation was observed.7. Gastric MALT lymphoma, gastric adenoma, and gastric carcinoid did not develop concomittantly. Rank orders of the number of H.pylori and serum gastrin level was carcinoid > adenoma > MALT lymphoma, whereas that of gastric acid secretion was MALT lymphoma > adenoma > carcinoid.8. Host factors such as capacity of acid secretion and hormone secretion, and immunological responses may be important for deciding the occurence of various disease phenotypes. Less