Fox J G, Yan L, Shames B, Campbell J, Murphy J C, Li X
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge 02139, USA.
Infect Immun. 1996 Sep;64(9):3673-81. doi: 10.1128/iai.64.9.3673-3681.1996.
Helicobacter hepaticus has been associated with naturally occurring hepatitis in certain inbred strains of mice, and in A/JCr mice it has been linked to the development of hepatic adenomas and adenocarcinomas. H. hepaticus was orally inoculated into 30 axenic, outbred female mice, and the mice were studied longitudinally to fulfill Koch's postulates and to ascertain the pathogenic potential of the organism under defined germfree conditions. Ten cage contact mice were also housed in the same germfree isolator to study transmission patterns, and 10 germfree mice were maintained in separate isolators as controls. Mice serially euthanized from 3 weeks through 24 months postinoculation (p.i.) were surveyed by culture and PCR for H. hepaticus in liver and intestinal tissues. Tissues were analyzed for histopathological changes, and sera were assayed for the presence of immunoglobulin G antibody to H. hepaticus and changes in the liver enzyme alanine aminotransferase. Inoculated mice and cage contact mice were persistently infected with H. hepaticus as identified by culture and PCR, in both the intestine and, less frequently, the liver, for the duration of the 2-year study. Animals developed persistent chronic hepatitis, and in some animals enterocolitis was noted. Hepatocellular carcinoma was diagnosed in one H. hepaticus-infected mouse. The level of H. hepaticus serum antibody was highest in experimentally infected mice at 12 to 18 months p.i.; this corresponded in general to the time interval when the highest levels of alanine aminotransferase were recorded. Although cage contact mice became persistently infected with H. hepaticus, lesions were less severe and the levels of serological biomarkers utilized in the study were lower. The H. hepaticus-infected mouse will provide an ideal model to study putative bacterial virulence determinants and how they interact with the host to induce chronic inflammation and tumorigenesis.
肝螺杆菌与某些近交系小鼠的自然发生性肝炎有关，在A/JCr小鼠中，它与肝腺瘤和腺癌的发生有关。将肝螺杆菌经口接种到30只无菌、远交系雌性小鼠体内，并对这些小鼠进行纵向研究，以满足科赫法则，并确定该生物体在特定无菌条件下的致病潜力。还将10只笼接触小鼠饲养在同一个无菌隔离器中以研究传播模式，另外10只无菌小鼠饲养在单独的隔离器中作为对照。对接种后3周直至24个月连续安乐死的小鼠，通过培养和PCR检测肝脏和肠道组织中的肝螺杆菌。分析组织的组织病理学变化，并检测血清中抗肝螺杆菌免疫球蛋白G抗体的存在以及肝酶丙氨酸转氨酶的变化。在为期2年的研究期间，通过培养和PCR鉴定，接种小鼠和笼接触小鼠在肠道以及较少情况下在肝脏中持续感染肝螺杆菌。动物出现持续性慢性肝炎，在一些动物中还观察到小肠结肠炎。在一只感染肝螺杆菌的小鼠中诊断出肝细胞癌。肝螺杆菌血清抗体水平在接种后12至18个月的实验感染小鼠中最高；这通常与记录到丙氨酸转氨酶最高水平的时间间隔相对应。尽管笼接触小鼠持续感染肝螺杆菌，但病变较轻，研究中使用的血清生物标志物水平较低。感染肝螺杆菌的小鼠将为研究假定的细菌毒力决定因素以及它们如何与宿主相互作用以诱导慢性炎症和肿瘤发生提供理想模型。
