Long-term Evaluation of Mouse Model Infected with Helicobacter pylori and Influence of Helicobacter pylori Infection on Gastric Carcinogenesis

장기 Helicobacter pyori 감염 마우스 모델 수립과 위암 발생에 미치는 영향

Kim, Sung-Woo;Cha, Choong-Keun;Han, Sang-Uk;Kim, Young-Bae;Lee, Won-Heung;Joo, Hee-Jae;Cho, Yong-Kwan;Cho, Sung-Won;Kim, Myung-Wook;Hahm, Ki-Baik
김성우;차충근;한상욱;김영배;이원홍;주희재;조용관;조성원;김명욱;함기백

  • Published : 20020100

Abstract

Background/Aims: This study was aimed to evaluate the long-term outcome of Helicobacter pylori (H. pylori) infection in mouse model and to know the influence of H. pylori infection on gastric carcinogenesis. Methods: Four-week-old specific pathogen free C57BL/6 mice (n=115) were infected with SS1, the mouse-adapted H. pylori strain. In the 4, 8, 16, 24, 36, 50 and 80 weeks after the bacterial inoculation, the H. pylori-infected mice were sacrificed. Results: After 80 weeks of infection, most of H. pylori-infected mice developed hyperplastic gastritis, but did not show any evidence of adenoma, dysplasia or carcinoma. Proliferating cell nuclear antigen-positive cells were most abundant at 50 weeks and tended to decrease at 80 weeks. Apoptosis was noted at 8 weeks after H. pylori infection, showing 7-8 apoptotic cells/high power field and tended to increase with the lapse of time. Normally observed neutral mucin was decreased with the lapse of time and it was remarkably decreased at 50 weeks after H. pylori infection. However, acidic mucin was remarkably noted from 50 weeks after the infection. Conclusions: SS1-infected mice seem to be suitable for H. pylori-related research and H. pylori itself does not induce gastric cancer in normal wild-type mice model in a long-term study, which could be explained by the balance between cell proliferation and apoptosis.

목 적 : 본 연구에서는 마우스를 이용해 H. pylori 감염 모델을 수립하고 감염 후 80주까지 연속적으로 병리학적 변화를 관찰하여 마우스 모델에서 H. pylori 감염이 위암을 유발할 수 있는가를 알아보고자 하였다. 대상 및 방법 : 4주령의 specific pathogen free C57BC/6 (n=115)에게 H. pylori를 주입하였다. 시술 후 H. pylori를 감염시킨 마우스를 각각 4주, 8주, 16주 후에 10마리씩을, 24주, 36주, 50주 후에 20마리씩을, 80주 후에 25마리를 희생시켰으며 대조군에서도 같은 시기마다 각각 5마리씩을 희생시켰다. 결 과 : H. pylori 감염군에서 80주까지 선종, 이형성 또는 암화의 증거는 전혀 관찰되지 않았으나 위벽이 비후되어 있었다. PCNA 양성 세포는 감염 후 50주째에 최고조에 달하며 80주째에는 다소 감소되는 경향을 보였다. H. pylori 감염 후에는 고배율 시야당 7-8개 정도의 세포사멸을 관찰할 수 있었고, 시간 경과에 따라 증가하는 양상을 보였다. H. pylori 감염 후 중성 점액은 현저하게 감소되는 반면에 산성 점액은 현저하게 증가되는 변화를 관찰할 수 있었다. 결 론 : C57BL/6 마우스 모델은 H.pylori 감염에 따른 위병변을 연구할 수 있는 우수한 모델임을 밝혀냈으며, 이들의 장기 관찰 결과 H. pylori는 정상 야생형 마우스에서는 위암을 유발시키지 않는다는 사실과 위암을 유발시키기 위해서는 세포증식과 세포사멸 간의 균형이 중요하다는 사실을 밝힐 수 있었다.

Keywords

References

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