Progression of chronic hepatitis and preneoplasia in Helicobacter hepaticus-infected A/JCr mice
Progression of chronic hepatitis and preneoplasia in Helicobacter hepaticus-infected A/JCr mice
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DOI：
10.1080/01926230490524247
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发表时间：
2004-11-01
影响因子：
1.5
通讯作者：
Fox, JG
中科院分区：
文献类型：
--
作者：
Rogers, AB;Boutin, SR;Fox, JG
肝螺杆菌感染可诱导A/JCr小鼠持续性炎症和肝癌，并可作为与病毒性肝炎和H.慢性胃炎在这里，我们描述了A/JCr小鼠感染H.肝我们对母鼠和/或出生后的幼鼠进行了妊娠内接种，并在3、6或12个月时对后代进行了评价。在3周龄或之前感染的小鼠，但在12周龄时未感染，发生疾病。雄性小鼠受影响最大，但表现出双峰模式的易感性。雄性表现出小叶坏死性肉芽肿和界面（慢性活动性）肝炎，而雌性通常发展为门静脉内（慢性持续性）肝炎。门静脉炎症缓慢进展，12个月时出现三级淋巴结。肝细菌负荷和癌前病变，包括透明和虎斑样细胞灶的细胞改变，与小叶性肝炎的严重程度相关。没有肝外替代疾病标志物可靠地预测个体肝炎分级。总之，性别和细菌暴露时间是H。肝病结局。肝内炎症是由局部信号驱动的，其特征是强烈但非杀菌的免疫反应。对慢性肝炎进展的持续研究可能揭示降低肝细胞癌风险的治疗靶点。
Helicobacter hepaticus infection induces sustained inflammation and carcinoma of the liver in A/JCr mice, and serves as a model of human cancers associated with viral hepatitis and H. pylori chronic gastritis. Here we describe the pathogenesis of premalignant disease in A/JCr mice infected with H. hepaticus. We inoculated dams intragestationally and/or pups postnatally, and evaluated offspring at 3, 6, or 12 months. Mice infected at or before 3 weeks of age, but not at 12 weeks, developed disease. Male mice were most affected, but expressed a bimodal pattern of susceptibility. Males exhibited lobular necrogranulomatous and interface (chronic active) hepatitis, while females usually developed intraportal (chronic persistent) hepatitis. Portal inflammation was slowly progressive, with tertiary lymphoid nodule development by 12 months. Hepatic bacterial load and preneoplastic lesions, including clear and tigroid cell foci of cellular alteration, were correlated with lobular hepatitis severity. No extrahepatic surrogate disease marker reliably predicted individual hepatitis grade. In conclusion, gender and bacterial exposure timing are key determinants of H. hepaticus disease outcomes. Intrahepatic inflammation is driven by local signals characterized by a vigorous but nonsterilizing immune response. Continued study of chronic hepatitis progression may reveal therapeutic targets to reduce the risk of hepatocellular carcinoma.