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Mechanism of interleukin-6 induction by intraperitoneal administration of carbon tetrachloride and its effect on hepatic injury

四氯化碳腹腔注射白细胞介素6的诱导机制及其对肝损伤的影响

基本信息

批准号：
18590120
负责人：
HOJO Hiroshi
金额：
$ 2.32万
依托单位：
Showa Pharmaceutical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

Carbon tetrachloride has been used as a model compound for studying hepatotoxicity. We previously demonstrated that a high level of interleukin (IL)-6 was induced in the early period after carbon tetrachloride administration via the intraperitoneal or subcutaneous mute, but not via the oral mute, in rats and it was produced at least partially by peritoneal cells in the serous membrane of the peritoneum through various inflammatory factors. In the present study we examined the mechanisms of IL-6 production and up-regulation of protective proteins by endogenously induced IL-6. Levels of inflammatory factors such as IL-la, IL-1B, tumor necrosis factor-a and pmstaglandin E_2 were increased and number of peritoneal cells was decreased in the peritoneum immediately after intraperitoneal carbon tetrachloride administration, and both increase in inflammatory factors and lass of cells were reduced as the vehicle-to-carbon tetrachloride was increased. It was considered that carbon tetrachloride … More dissolved in a small dose of vehicle easily reacted with membrane lipid components and caused activation or lysis of peritoneal cells to release inflammatory factors. IL-1a seems to contribute to IL-6 production most effectively among the inflammatory factors, judging from its high IL-6-inducing potency and concentration in the peritoneal exudate. Heme oxygenase-1 (HO-1) was induced more in rats administered carbon tetrachloride intraperitoneally compared with orally ; while, expression of heat shock protein (HSP) 72 and HSP90 were increased to similar extents in both experimental groups. The fact that the HO-1 expression was partially reduced by pretreatment with anti-rat IL-6 antibody shows that hepatic HO-1. is up-regulated by endogenously induced by .IL-6, in addition to its up-regulation by heme derived from cytochrome P450 which has already been reported. Since HO-1 is known to reduce tissue injuries, the present findings should be taken into consideration during the analysis of data using the carbon tetrachloride-induced liver injury model. Less

四氯化碳已被用作研究肝毒性的模型化合物。我们以前证明，高水平的白细胞介素（IL）-6诱导后的早期通过腹腔内或皮下注射静音，但不是通过口服静音，在大鼠中，它至少部分产生的腹膜细胞在腹膜浆膜通过各种炎症因子。在本研究中，我们研究了内源性诱导的IL-6产生和上调保护蛋白的机制。腹腔注射CCl 4后即刻，腹腔内IL-1a、IL-1B、TNF-α和pM_2E_2等炎性因子水平升高，腹腔内细胞数减少，且随着CCl 4浓度的增加，炎性因子的升高和细胞数减少均减少。据认为，四氯化碳 ...更多信息溶解在小剂量的载体中容易与膜脂质组分反应并引起腹膜细胞的活化或溶解以释放炎性因子。IL-1a在炎症因子中似乎最有效地促进IL-6的产生，从其高IL-6诱导效力和腹膜渗出液中的浓度来判断。腹腔注射四氯化碳组血红素氧合酶-1（HO-1）的表达明显高于口服组，热休克蛋白（HSP）72和HSP 90的表达在两个实验组中的增加程度相似。用抗大鼠IL-6抗体预处理可部分降低HO-1的表达，这一事实表明肝HO-1.除了已经报道的来源于细胞色素P450的血红素的上调外，IL-6的内源性诱导也上调了IL-6的表达。由于HO-1是已知的，以减少组织损伤，目前的研究结果应考虑到数据分析过程中使用四氯化碳诱导的肝损伤模型。少