Nakamura Masahiko, Murayama Somay Yamagata, Serizawa Hiroshi, Sekiya Yukie, Eguchi Masahiro, Takahashi Shinichi, Nishikawa Kaori, Takahashi Tetsufumi, Matsumoto Tsukasa, Yamada Haruki, Hibi Toshifumi, Tsuchimoto Kanji, Matsui Hidenori
School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Infect Immun. 2007 Mar;75(3):1214-22. doi: 10.1128/IAI.01459-06. Epub 2006 Dec 28.
Both Helicobacter pylori and "Candidatus Helicobacter heilmannii" infections are associated with peptic ulcers, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue (MALT) lymphomas. However, good animal models of H. pylori clinical diseases are rare. In this study, we aimed to establish an animal model of "Candidatus Helicobacter heilmannii" gastric MALT lymphoma. We used a urease-positive gastric mucosal and mucus homogenate from a cynomolgus monkey maintained in C57BL/6 mouse stomachs. The bacterium in the homogenate was identified as "Candidatus Helicobacter heilmannii" based on a DNA sequence analysis of the 16S rRNA and urease genes. Mucosal and mucus homogenates were used to inoculate C57BL/6 mice, which were then examined for 24 months. We observed a gradual increase in the surface area of protrusive lesions in almost all infected C57BL/6 mouse fundic stomachs 6 months after infection. Light microscopic observations revealed an accumulation of B lymphocytes along with destruction of glandular elements and the presence of lymphoepithelial lesions consistent with low-grade MALT lymphomas. Electron microscopic observation revealed numerous "Candidatus Helicobacter heilmannii" bacilli in the fundic glandular lumen, the intracellular canaliculi, and the cytoplasm of intact cells, as well as damaged parietal cells. In conclusion, "Candidatus Helicobacter heilmannii" induced gastric MALT lymphomas in almost 100% of infected C57BL/6 mice after a 6-month period associated with the destruction of parietal cells.
幽门螺杆菌和“海氏螺杆菌(暂定名)”感染均与消化性溃疡、胃腺癌及胃黏膜相关淋巴组织(MALT)淋巴瘤有关。然而,幽门螺杆菌临床疾病的优良动物模型却很罕见。在本研究中,我们旨在建立一种“海氏螺杆菌(暂定名)”胃MALT淋巴瘤动物模型。我们使用了来自一只饲养于C57BL/6小鼠胃内的食蟹猴的脲酶阳性胃黏膜及黏液匀浆。基于对16S rRNA和脲酶基因的DNA序列分析,匀浆中的细菌被鉴定为“海氏螺杆菌(暂定名)”。用黏膜及黏液匀浆接种C57BL/6小鼠,随后对其进行24个月的观察。感染6个月后,我们观察到几乎所有受感染的C57BL/6小鼠胃底部突出性病变的表面积逐渐增加。光学显微镜观察显示B淋巴细胞聚集,伴有腺泡结构破坏以及与低级别MALT淋巴瘤一致的淋巴上皮病变。电子显微镜观察显示胃底腺管腔、细胞内小管及完整细胞的细胞质中有大量“海氏螺杆菌(暂定名)”杆菌,同时还有受损的壁细胞。总之,“海氏螺杆菌(暂定名)”在6个月内导致几乎100%受感染的C57BL/6小鼠发生胃MALT淋巴瘤,并伴有壁细胞破坏。
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