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辐射对大鼠肝脏趋化因子基因表达的影响:体内和体外研究

Effect of radiation on gene expression of rat liver chemokines: in vivo and in vitro studies.

作者信息

Moriconi Federico, Christiansen Hans, Raddatz Dirk, Dudas Joszef, Hermann Robert Michael, Rave-Fränk Margret, Sheikh Nadeem, Saile Bernhard, Hess Clemens Friedrich, Ramadori Giuliano

机构信息

Department of Gastroenterology and Endocrinology, Gottingen University, 37075 Goettingen, Germany.

出版信息

Radiat Res. 2008 Feb;169(2):162-9. doi: 10.1667/RR1006.1.

Abstract

The aim of the study was to analyze the effect of a single irradiation on chemokine gene expression in the rat liver and in isolated rat hepatocytes. RNA extracted from livers and from hepatocytes within the first 48 h after irradiation was analyzed by real-time PCR and the Northern blot assay. The chemokine concentrations in the serum of irradiated rats were measured quantitatively by ELISA. A significant radiation-induced increase of CINC1, IP10, MCP1, MIP3alpha, MIP3beta, MIG and ITAC gene expression could be detected at the RNA level in the liver. CINC1, MCP1 and IP10 serum levels were significantly increased. In rat hepatocytes in vitro, only MIP3alpha showed a radiation-induced increase in expression, while CINC1, IP10, MIP3beta, MIG, MIP1alpha, ITAC and SDF1 RNA levels were significantly down-regulated. However, incubation of irradiated hepatocytes in vitro with either TNF-alpha, IL1beta, or IL6 plus TNF-alpha led to up-regulation of MCP1, IP10 and MCP1 or CINC1 and MIP3beta, respectively. Irradiation of the liver induces up-regulation of the genes of the main proinflammatory chemokines, probably through the action of locally synthesized proinflammatory cytokines. The reason for the lack of liver inflammation in this model has still to be clarified.

摘要

本研究的目的是分析单次照射对大鼠肝脏及分离的大鼠肝细胞中趋化因子基因表达的影响。通过实时聚合酶链反应(PCR)和Northern印迹分析,对照射后48小时内从肝脏和肝细胞中提取的RNA进行分析。采用酶联免疫吸附测定法(ELISA)定量检测受照射大鼠血清中的趋化因子浓度。在肝脏的RNA水平上,可检测到辐射诱导的CINC1、IP10、MCP1、MIP3α、MIP3β、MIG和ITAC基因表达显著增加。CINC1、MCP1和IP10的血清水平显著升高。在体外培养的大鼠肝细胞中,只有MIP3α的表达显示出辐射诱导的增加,而CINC1、IP10、MIP3β、MIG、MIP1α、ITAC和SDF1的RNA水平则显著下调。然而,体外将受照射的肝细胞与肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL1β)或白细胞介素-6加TNF-α孵育,分别导致MCP1、IP10和MCP1或CINC1和MIP3β的上调。肝脏照射可能通过局部合成的促炎细胞因子的作用,诱导主要促炎趋化因子基因的上调。该模型中缺乏肝脏炎症的原因仍有待阐明。

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