首页> 外文期刊>American Journal of Physiology >Hepcidin and hemojuvelin gene expression in rat liver damage: in vivo and in vitro studies.
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Hepcidin and hemojuvelin gene expression in rat liver damage: in vivo and in vitro studies.

机译:Hepcidin和hemojuvelin基因在大鼠肝损伤中的表达:体内和体外研究。

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摘要

In this work, we used two rat models, partial hepatectomy (PH) and CCl(4) administration, to study the changes in iron pathways in response to hepatic damage. Liver injury induced changes in the hepatic gene expression of hepcidin, hemojuvelin (Hjv), several other proteins of iron metabolism, and several cytokines such as IL-1beta, IL-6, TNF-alpha, and IFN-gamma. Hepcidin gene expression was upregulated between 4 and 8 h with a maximum up to 16 h after surgery. However, Hjv gene expression was downregulated at the same time. An early upregulation of hepcidin (3 h) and downregulation of Hjv gene expression was found after CCl(4) administration. Transferrin receptor 1 and ferritin H gene expression was upregulated, whereas ferroportin 1 gene expression was downregulated. Hepatic IL-6 gene expression was upregulated early after PH and reached maximum 8 h after the PH. In CCl(4)-induced liver injury, IL-6, IL-1beta, TNF-alpha, and IFN-gamma upregulation were found at the maximum 12 h after the administration of the toxin. Treatment of isolated rat hepatocytes with IL-6 and, to a lesser extent, with IL-1beta but not with TNF-alpha or IFN-gamma dose dependently upregulated hepcidin and downregulated Hjv gene expression. In hepatic damage, changes of the hepatic gene expression of the main proteins involved in iron metabolism may be induced by locally synthesized mediators.
机译:在这项工作中,我们使用了两种大鼠模型,部分肝切除术(PH)和CCl(4)给药,研究了铁通道对肝损伤的响应变化。肝损伤诱导了肝素,血juvelin(Hjv),铁代谢的其他几种蛋白质以及几种细胞因子(例如IL-1beta,IL-6,TNF-α和IFN-γ)的肝基因表达变化。 Hepcidin基因表达在手术后4至8 h之间上调,最大可达16 h。但是,Hjv基因表达同时被下调。 CCl(4)管理后,发现了铁调素的早期上调(3小时)和Hjv基因表达的下调。转铁蛋白受体1和铁蛋白H基因表达上调,而铁转运蛋白1基因表达下调。 PH后早期肝IL-6基因表达上调,PH后8h达到最大。在CCl(4)诱导的肝损伤中,在给予毒素后的最大12小时内发现IL-6,IL-1beta,TNF-α和IFN-γ上调。用IL-6以及较小程度地用IL-1beta而不是TNF-α或IFN-γ剂量处理离体大鼠肝细胞,可依赖地上调铁调素和下调Hjv基因表达。在肝损伤中,可能由局部合成的介体诱导参与铁代谢的主要蛋白的肝基因表达变化。

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