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Persistent hepatitis and enterocolitis in germfree mice infected with Helicobacter hepaticus.

机译:感染了肝杆菌的无菌小鼠的持续性肝炎和小肠结肠炎。

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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.
机译:在某些近交系小鼠中,肝幽门螺杆菌与自然发生的肝炎有关,在A / JCr小鼠中,它与肝腺瘤和腺癌的发展有关。肝炎链球菌经口接种到30只缺氧的近交雌性小鼠中,并对小鼠进行纵向研究,以符合Koch的假设并确定该微生物在确定的无菌条件下的致病潜力。将十只笼接触小鼠也饲养在相同的无菌隔离器中,以研究传播方式,并将十只无菌小鼠作为对照放在不同的隔离器中。接种后3周至24个月对连续安乐死的小鼠(p.i.)进行培养和PCR检测,观察其在肝和肠组织中的肝嗜血杆菌。分析组织的组织病理学变化,并测定血清中是否存在针对肝H.的免疫球蛋白G抗体和肝酶丙氨酸氨基转移酶的变化。在为期2年的研究期间,无论是在肠道内还是在肝脏中,经培养和PCR鉴定,接种的小鼠和笼养型小鼠均持续感染肝炎链球菌(H. hepaticus)。动物发展为持续性慢性肝炎,并且在一些动物中发现了小肠结肠炎。在一只感染了肝菌的小鼠中诊断出肝细胞癌。在感染后的p.i. 12到18个月,肝炎肝菌血清抗体水平最高。这通常对应于记录最高水平的丙氨酸转氨酶的时间间隔。尽管笼子接触小鼠持续感染肝炎性肝炎,但病灶较轻,研究中使用的血清学生物标志物水平较低。感染了H. hepaticus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的模型。

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