Lipopolysaccharide-induced inflammatory liver injury in mice

Lipopolysaccharide-induced inflammatory liver injury in mice
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DOI:
10.1177/0023677215570087
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发表时间:
2015-04-01
期刊:
影响因子:
2.4
通讯作者:
Weiskirchen, R.
Weiskirchen, R.
中科院分区:
医学4区
文献类型:
--
作者:
Hamesch, K.;Borkham-Kamphorst, E.;Weiskirchen, R.

文献摘要

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腹腔注射脂多糖(LPS)或与其他肝毒素联合应用是一种在世界各地广泛应用的诱发啮齿动物全身和肝脏炎症的实验模型。内毒素是由内毒素结合蛋白识别的。这个复合体与淋巴细胞抗原96(MD2)和模式识别受体CD14结合在一起,与Toll样受体家族的成员结合。激活的受体复合体反过来将信号传导到具有良好特性的细胞内级联,从而导致一个多方面的细胞内反应网络,最终导致炎症。其中最突出的是核因子-B途径的激活和大量炎性细胞因子的产生。尽管脂多糖的应用通常很容易进行,但在注射溶液的制备或对动物的处理方面的意外变化可能会影响特定实验的重复性或结果。在这里,我们提出了一种标准化的方案,允许在小鼠中诱导高度可重复性的急性肝炎。此外,还给出了所产生的炎症反应的适当读数的例子。
The intraperitoneal application of lipopolysaccharide (LPS) alone or in combination with other hepatotoxins is an experimental model for inducing systemic and hepatic inflammation in rodents applied worldwide. The endotoxin is recognized by the LPS-binding protein. This complex binds together with the lymphocyte antigen 96 (MD2) and the pattern-recognition receptor CD14 to members of the toll-like receptor family. The activated receptor complex in turn transduces signals to well characterized intracellular cascades that result in a multifaceted network of intracellular responses ending in inflammation. The most prominent among these is the activation of the NF-B pathway and the production of a multitude of inflammatory cytokines. Although the application of LPS is in general easy to perform, unintended variations in preparation of the injection solution or in handling of the animals might affect the reproducibility or the outcome of a specific experiment. Here, we present a well-standardized protocol that allows for an induction of highly reproducible acute hepatic inflammation in mice. Furthermore, examples of appropriate readouts for the resulting inflammatory response are given.