肿瘤坏死因子α（TNFα）是小鼠胆汁淤积诱导的肝纤维化所必需的。
TNFalpha is required for cholestasis-induced liver fibrosis in the mouse.
作者信息
Gäbele Erwin, Froh Matthias, Arteel Gavin E, Uesugi Takehiko, Hellerbrand Claus, Schölmerich Jürgen, Brenner David A, Thurman Ronald G, Rippe Richard A
机构信息
Laboratory of Hepatobiology and Toxicology, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
出版信息
Biochem Biophys Res Commun. 2009 Jan 16;378(3):348-53. doi: 10.1016/j.bbrc.2008.10.155. Epub 2008 Nov 6.
TNFalpha, a mediator of hepatotoxicity in several animal models, is elevated in acute and chronic liver diseases. Therefore, we investigated whether hepatic injury and fibrosis due to bile duct ligation (BDL) would be reduced in TNFalpha knockout mice (TNFalpha-/-). Survival after BDL was 60% in wild-type mice (TNFalpha+/+) and 90% in TNFalpha-/- mice. Body weight loss and liver to body weight ratios were reduced in TNFalpha-/- mice compared to TNFalpha+/+ mice. Following BDL, serum alanine transaminases (ALT) levels were elevated in TNFalpha+/+ mice (268.6+/-28.2U/L) compared to TNFalpha-/- mice (105.9U/L+/-24.4). TNFalpha-/- mice revealed lower hepatic collagen expression and less liver fibrosis in the histology. Further, alpha-smooth muscle actin, an indicator for activated myofibroblasts, and TGF-beta mRNA, a profibrogenic cytokine, were markedly reduced in TNFalpha-/- mice compared to TNFalpha+/+ mice. Thus, our data indicate that TNFalpha induces hepatotoxicity and promotes fibrogenesis in the BDL model.
肿瘤坏死因子α（TNFα）是多种动物模型中肝毒性的介质，在急性和慢性肝病中水平升高。因此，我们研究了在TNFα基因敲除小鼠（TNFα-/-）中，胆管结扎（BDL）所致的肝损伤和肝纤维化是否会减轻。BDL后，野生型小鼠（TNFα+/+）的存活率为60%，而TNFα-/-小鼠为90%。与TNFα+/+小鼠相比，TNFα-/-小鼠的体重减轻以及肝重与体重之比降低。BDL后，TNFα+/+小鼠的血清丙氨酸转氨酶（ALT）水平（268.6±28.2U/L）高于TNFα-/-小鼠（105.9U/L±24.4）。组织学检查显示，TNFα-/-小鼠的肝脏胶原蛋白表达较低，肝纤维化程度较轻。此外，与TNFα+/+小鼠相比，TNFα-/-小鼠中活化肌成纤维细胞的标志物α-平滑肌肌动蛋白以及促纤维化细胞因子转化生长因子β（TGF-β）的mRNA水平显著降低。因此，我们的数据表明，在BDL模型中，TNFα诱导肝毒性并促进纤维化形成。
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