TNFalpha is required for cholestasis-induced liver fibrosis in the mouse.
TNFalpha is required for cholestasis-induced liver fibrosis in the mouse.
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DOI：
10.1016/j.bbrc.2008.10.155
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发表时间：
2009-01-16
影响因子：
3.1
通讯作者：
Rippe, Richard A.
中科院分区：
文献类型：
--
作者：
Gaebele, Erwin;Froh, Matthias;Arteel, Gavin E.;Uesugi, Takehiko;Hellerbrand, Claus;Schoelmerich, Juejrgen;Brenner, David A.;Thurman, Ronald G.;Rippe, Richard A.
关键词：
TNFα是几种动物模型中肝毒性的介质，在急性和慢性肝病中升高。因此，我们研究了在TNFα敲除小鼠（TNFα−/−）中，胆管结扎（BDL）引起的肝损伤和纤维化是否会减少。BDL后的存活率在野生型小鼠（TNFα+/+）中为60%，在TNFα−/−小鼠中为90%。与TNFα+/+小鼠相比，TNFα−/−小鼠的体重减轻和肝脏/体重比降低。BDL后，与TNFα-/-小鼠（105.9 U/L ± 24.4）相比，TNFα+/+小鼠（268.6 ± 28.2 U/L）的血清丙氨酸氨基转移酶（ALT）水平升高。TNFα −/−小鼠在组织学上显示出较低的肝胶原表达和较少的肝纤维化。此外，与TNFα+/+小鼠相比，TNFα−/−小鼠中的α-平滑肌肌动蛋白（活化肌成纤维细胞的指标）和TGF-β mRNA（促纤维化细胞因子）显著减少。因此，我们的数据表明，TNFα诱导肝毒性和促进BDL模型中的纤维化。
TNFα, 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 TNFα knockout mice (TNFα−/−). Survival after BDL was 60% in wild-type mice (TNFα+/+) and 90% in TNFα−/− mice. Body weight loss and liver to body weight ratios were reduced in TNFα−/− mice compared to TNFα+/+ mice. Following BDL, serum alanine transaminases (ALT) levels were elevated in TNFα+/+ mice (268.6 ± 28.2 U/L) compared to TNFα−/− mice (105.9 U/L ± 24.4). TNFα −/− mice revealed lower hepatic collagen expression and less liver fibrosis in the histology. Further, α-smooth muscle actin, an indicator for activated myofibroblasts, and TGF-β mRNA, a profibrogenic cytokine, were markedly reduced in TNFα−/− mice compared to TNFα+/+ mice. Thus, our data indicate that TNFα induces hepatotoxicity and promotes fibrogenesis in the BDL model.
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