Animal model of stomach carcinogenesis in mice infected with Helicobacter pylori

幽门螺杆菌感染小鼠胃癌动物模型

• 批准号: 10680779
• 负责人: KITA Masakazu
• 金额: $ 0.7万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10680779/
• 关键词: Helicobacter; infection; cancer; ENNO; mouse; 胃癌; マウスモデル

It is now generally accepted that Helicobacter pylori infection is a major cause of chronic gastritis and peptic ulcers. Although epidemiological studies have indicated that H. pylori infection plays a crucial role in gastric carcinogenesis in human, there have been few reports demonstrating a relation between H. pylori and stomach cancer in animal models. In the present study, we first examined the colonizing abilities of eight H. pylori strains in order to select H. pylori strain which could colonize the mouse stomach. Three strains (ATCC43504,CPY2052,and HPK127) colonized C57BL/6 mice, and only CPY2052-infected mice developed a severe gastric inflammation in the lamina propria and erosions in the gastric epithelium 15 months after infection. Secondly, the effect of H. pylori infection on N-methyl-N-nitro-N-nitrosoguanidine (ENNG)-induced gastric cancer was studied using a mouse model. Five-week-old male C57BL/6 mice were divided into four groups of 20-30 animals each and challenged with H. pylori (H. felis), ENNG, a combination of H. pylori (H. felis) and ENNG, or neither of them. Five to 20 animals from each group were sacrificed at 20 and 50 weeks after H. pylori (H. felis) inoculation, and histopathological changes in their stomachs were examined. The incidence of adenomatous hyperplasia in the combination group was significantly higher than that in the ENNG group (p<0.05). These results suggest that H. pylori infection enhances the carcinogenic action of ENNG. This mouse model may be useful for the study of pathogenesis, the screening of novel therapeutic agents, and the development of vaccines.

目前普遍认为幽门螺杆菌感染是慢性胃炎和消化性溃疡的主要原因。尽管流行病学研究表明幽门螺杆菌感染在人类胃癌发生中起着至关重要的作用，但在动物模型中证明幽门螺杆菌与胃癌之间关系的报道却很少。在本研究中，我们首先检测了8株H. pylori菌株的定植能力，以筛选出能够在小鼠胃中定植的H. pylori菌株。三种菌株（ATCC43504、CPY2052 和 HPK127）定植于 C57BL/6 小鼠，只有 CPY2052 感染的小鼠在感染后 15 个月出现严重的固有层胃炎症和胃上皮糜烂。其次，利用小鼠模型研究了幽门螺杆菌感染对N-甲基-N-硝基-N-亚硝基胍（ENNG）诱导的胃癌的影响。将五周大的雄性 C57BL/6 小鼠分为四组，每组 20-30 只动物，并用幽门螺杆菌 (H. felis)、ENNG、幽门螺杆菌 (H. felis) 和 ENNG 的组合进行攻击，或他们都没有。接种幽门螺杆菌（H. felis）后20周和50周处死每组5至20只动物，检查其胃的组织病理学变化。联合组腺瘤增生发生率显着高于ENNG组（p<0.05）。这些结果表明幽门螺杆菌感染增强了 ENNG 的致癌作用。该小鼠模型可用于发病机制的研究、新型治疗剂的筛选和疫苗的开发。

项目成果

Yamaoka Y, Kodama T, Kite M, et al.: "Relation between clinical presentation, Helicobacter pylori density, interleukin-1beta and 8 production, and cagA status"Gut. 45. 804-811 (1999)

Yamaoka Y、Kodama T、Kite M 等人：“临床表现、幽门螺杆菌密度、白细胞介素 1β 和 8 的产生以及 cagA 状态之间的关系”Gut。

Yamaoka Y, Kodama T, Kita M, Imanishi J, Kashima K, Graham DY.: "Relation between clinical presentation, Helicobacter pylori density, interleukin 1beta and 8 production, and cagA status."Gut. 45. 804-811 (1999)

Yamaoka Y、Kodama T、Kita M、Imanishi J、Kashima K、Graham DY.：“临床表现、幽门螺杆菌密度、白介素 1β 和 8 产生以及 cagA 状态之间的关系。”肠道。

Tanahashi T, Kite M, et al.: "Cytokine expression and production by purified Helicobacter pylori urease in human gastric epithelial cells"Infect.Immun.. 68. 664-671 (2000)

Tanahashi T、Kite M 等：“人胃上皮细胞中纯化的幽门螺杆菌脲酶的细胞因子表达和产生”Infect.Immun.. 68. 664-671 (2000)

Sawai N, Kita M, Kodama T, Tanahashi T, Yamaoka Y, Tagawa Y, Iwakura Y, Imanishi J.: "Role of gamma interferon in Helicobacter pylori-induced gastric inflammatory responses in a mouse model."Infec.Immun.. 67(1). 279-285 (1999)

Sawai N、Kita M、Kodama T、Tanahashi T、Yamaoka Y、Takawa Y、Iwakura Y、Imanishi J.：“γ 干扰素在小鼠模型中幽门螺杆菌诱导的胃炎症反应中的作用。”Infec.Immun.. 67

Sawai N, Kita M et al.: "Role of gamma interferon in Helicobacter pylori-induced gastric inflammatory responses in a mouse model" Infection and Immunity. 67(1). 279-285 (1999)

Sawai N、Kita M 等人：“γ 干扰素在小鼠模型中幽门螺杆菌诱导的胃炎症反应中的作用”感染和免疫。