Although various animal models have been developed to clarify gastric carcinogenesis, apparent mechanism of gastric cancer was not clarified in recent years. Since the recognition of the pathogenicity of Helocobacter ...Although various animal models have been developed to clarify gastric carcinogenesis, apparent mechanism of gastric cancer was not clarified in recent years. Since the recognition of the pathogenicity of Helocobacter pylori（H pylori）, several animal models with H pylori infection have been developed to confirm the association between Hpylori and gastric cancer. Nonhuman primate and rodent models were suitable for this study. Japanese monkey model revealed atrophic gastritis and p53 mutation after long-term infection of Hpylori. Mongolian gerbil model showed the development of gastric carcinoma with H pylori infection alone, as well as with combination of chemical carcinogens, such as N-methyl- N-nitrosourea and N-methyl-N-nitro-N＇-nitrosoguanidine. The histopathological changes of these animal models after H pylori inoculation are closely similar to those in human beings with Hpylori infection. Eradication therapy attenuated the development of gastric cancer in Hpylori- infected Mongolian gerbil. Although several features of animal models differ from those seen in human beings, these experimental models provide a starting point for further studies to clarify the mechanism of gastric carcinogenesis as a result of Hpylon infection and assist the planning of eradication therapy to prevent gastric carcinoma.展开更多
AIM： To investigate whether chronic H pylori infection has the potential to induce pancreatitis in the Mongolian gerbil model, and whether it is dependent on an intact type Ⅳ secretion system. METHODS： Mongolian ge...AIM： To investigate whether chronic H pylori infection has the potential to induce pancreatitis in the Mongolian gerbil model, and whether it is dependent on an intact type Ⅳ secretion system. METHODS： Mongolian gerbils were infected with wild type （WT） H pylori type Ⅰ strain B128 or its isogenic mutant B128 △cag γ （defective type Ⅳ secretion）. After seven months of infection, H pylori was reisolated from antrum and corpus and Hpylori DNA was analyzed by seminested polymerase chain reaction （PCR）. Inflammation and histological changes were documented in the gastric antrum, corpus, and pancreas by immunohistochemistry. Cytokine mRNA, gastric pH, plasma gastrin, amylase, lipase, and glucose levels were determined. RESULTS： The H pylori infection rate was 95%. Eight infected animals, but none of the uninfected group, developed transmural inflammation and chronic pancreatitis. Extensive interstitial fibrosis and inflammation of the pancreatic lobe adjacent to the antrum was confirmed by trichrome stain, and immuno-histochemically. Pro-inflammatory cytokine mRNA was significantly increased in the antral mucosa of all infected gerbils. In the corpus, only cytokine levels of WT-infected animals andthose developing transmural inflammation and pancreatitis were significantly increased. Levels of lipase, but not glucose or amylase levels, were significantly reduced in the pancreatitis group. H pylori DNA was detected in infected antral and corpus tissue,but not in the pancreas CONCLUSION： H pylori infection is able to induce chronic pancreatitis in Mongolian gerbils independently of the type Ⅳ secretion system, probably by an indirect mechanism associated with a penetrating ulcer.展开更多
文摘Although various animal models have been developed to clarify gastric carcinogenesis, apparent mechanism of gastric cancer was not clarified in recent years. Since the recognition of the pathogenicity of Helocobacter pylori（H pylori）, several animal models with H pylori infection have been developed to confirm the association between Hpylori and gastric cancer. Nonhuman primate and rodent models were suitable for this study. Japanese monkey model revealed atrophic gastritis and p53 mutation after long-term infection of Hpylori. Mongolian gerbil model showed the development of gastric carcinoma with H pylori infection alone, as well as with combination of chemical carcinogens, such as N-methyl- N-nitrosourea and N-methyl-N-nitro-N＇-nitrosoguanidine. The histopathological changes of these animal models after H pylori inoculation are closely similar to those in human beings with Hpylori infection. Eradication therapy attenuated the development of gastric cancer in Hpylori- infected Mongolian gerbil. Although several features of animal models differ from those seen in human beings, these experimental models provide a starting point for further studies to clarify the mechanism of gastric carcinogenesis as a result of Hpylon infection and assist the planning of eradication therapy to prevent gastric carcinoma.
基金Supported by grants from the Deutsche Forschungsgemeinschaft (SFB576) to RH and (RI 972/3-1) to GRthe Federal Ministry of Education and Research (BMBF) (NGFN-2) to RHby US Public Health Service Grants P01 DK062041 and R01DK45729 to JLM
文摘AIM： To investigate whether chronic H pylori infection has the potential to induce pancreatitis in the Mongolian gerbil model, and whether it is dependent on an intact type Ⅳ secretion system. METHODS： Mongolian gerbils were infected with wild type （WT） H pylori type Ⅰ strain B128 or its isogenic mutant B128 △cag γ （defective type Ⅳ secretion）. After seven months of infection, H pylori was reisolated from antrum and corpus and Hpylori DNA was analyzed by seminested polymerase chain reaction （PCR）. Inflammation and histological changes were documented in the gastric antrum, corpus, and pancreas by immunohistochemistry. Cytokine mRNA, gastric pH, plasma gastrin, amylase, lipase, and glucose levels were determined. RESULTS： The H pylori infection rate was 95%. Eight infected animals, but none of the uninfected group, developed transmural inflammation and chronic pancreatitis. Extensive interstitial fibrosis and inflammation of the pancreatic lobe adjacent to the antrum was confirmed by trichrome stain, and immuno-histochemically. Pro-inflammatory cytokine mRNA was significantly increased in the antral mucosa of all infected gerbils. In the corpus, only cytokine levels of WT-infected animals andthose developing transmural inflammation and pancreatitis were significantly increased. Levels of lipase, but not glucose or amylase levels, were significantly reduced in the pancreatitis group. H pylori DNA was detected in infected antral and corpus tissue,but not in the pancreas CONCLUSION： H pylori infection is able to induce chronic pancreatitis in Mongolian gerbils independently of the type Ⅳ secretion system, probably by an indirect mechanism associated with a penetrating ulcer.
