Mechanism for gastric carcinogenesis by H.pylori infection

我们研究了新生胸腺切除BALB/c小鼠中幽门螺杆菌感染引起的各种肿瘤性病变的发生机制。出生后第3天行胸腺切除术，术后2个月口服幽门螺杆菌感染。将幽门螺杆菌感染BALB/c小鼠后，持续性感染的发生率较低，且胃粘膜炎症的发生率较低.相反，当出生后3天切除胸腺的BALB/c小鼠感染H. pylori时，所有小鼠均出现持续感染，并伴有明显的胃粘膜炎症.感染后3个月，胃窦粘膜发生肠上皮化生。4.切除胸腺的小鼠中，感染后6个月有10%的小鼠发生胃腺腺瘤。然而，即使在感染后1年也不能观察到胃癌.胸腺切除小鼠淋巴滤泡发育明显， 关于我们 感染后2个月存活，70%发生胃MALT淋巴瘤.在这些小鼠中，在感染后1年，在所有动物中约30%的动物中观察到胃类癌形成。血清胃泌素浓度为1450 × 96pg/ml，显著高于非感染组（116 × 10pg/ml）和未形成类癌的感染组（765 × 56pg/ml）（P <0.01）。此外，在用特异性胃泌素受体拮抗剂AG041R治疗的感染小鼠中，未发现类癌形成。胃MALT淋巴瘤、胃腺瘤和胃类癌未发生并发症。幽门螺杆菌数量和血清胃泌素水平的排序为类癌>腺瘤> MALT淋巴瘤，胃酸分泌的排序为MALT淋巴瘤>腺瘤>类癌.宿主因素如泌酸和激素分泌能力以及免疫应答可能对决定各种疾病表型的发生是重要的。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