Rogers Arlin B
Lineberger Comprehensive Cancer Center and Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA.
Methods Mol Biol. 2012;921:175-88. doi: 10.1007/978-1-62703-005-2_21.
Animal models are used to study complex host, microbial, and environmental influences associated with gastric Helicobacter infection. Evidence that gastric helicobacters are pathogenic in animals first came from ferrets. Felids, nonhuman primates, and many other species also harbor stomach helicobacters. Today, mice are preferred by most researchers for scientific investigation because of cost-efficiencies, rapid reproduction, choice of laboratory reagents, and availability of genetically engineered models. Infection with Helicobacter felis or H. pylori Sydney strain-1 in appropriate mouse strains produces disease with remarkable similarities to H. pylori in humans. Due to recent advances in genetic engineering, in vivo imaging, and system-wide genomics and proteomics, these models will become even more widespread in the future. Recently, it has been shown that extragastric infections can dramatically affect the severity of disease induced by gastric Helicobacter spp. through heterologous immunity. These models provide proof-of-principle for the "African enigma" wherein gastric cancer is underrepresented in low-lying tropical countries with concurrently high H. pylori and internal parasite prevalence. Helicobacter gastritis and carcinogenesis in mouse models may be augmented or ameliorated by other infectious agents depending on the character of the invoked immune response. Knowledge gained from the Human Microbiome Project and other investigations is certain to shed new light on the influence of extragastric bacterial, viral, fungal, and parasitic coinfections on H. pylori-associated peptic ulcer disease and gastric adenocarcinoma.
动物模型用于研究与胃幽门螺杆菌感染相关的复杂宿主、微生物和环境影响。胃幽门螺杆菌在动物中具有致病性的证据最早来自雪貂。猫科动物、非人灵长类动物和许多其他物种也携带胃幽门螺杆菌。如今，由于成本效益、繁殖速度快、实验室试剂的选择以及基因工程模型的可用性，小鼠成为大多数研究人员进行科学研究的首选。在合适的小鼠品系中感染猫幽门螺杆菌或幽门螺杆菌悉尼菌株1会引发与人类幽门螺杆菌感染极为相似的疾病。由于基因工程、体内成像以及全系统基因组学和蛋白质组学的最新进展，这些模型在未来将得到更广泛的应用。最近有研究表明，胃外感染可通过异源免疫显著影响胃幽门螺杆菌属引起的疾病严重程度。这些模型为“非洲之谜”提供了原理证明，即在幽门螺杆菌和体内寄生虫患病率同时较高的低洼热带国家，胃癌的发病率较低。根据所引发的免疫反应的特征，其他感染因子可能会增强或改善小鼠模型中的幽门螺杆菌胃炎和致癌作用。从人类微生物组计划和其他研究中获得的知识肯定会为胃外细菌、病毒、真菌和寄生虫合并感染对幽门螺杆菌相关消化性溃疡疾病和胃腺癌的影响带来新的启示。
