Antithrombin Insufficiency Promotes Susceptibility to Liver Tumorigenesis
Antithrombin Insufficiency Promotes Susceptibility to Liver Tumorigenesis
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DOI：
10.1016/j.jss.2018.11.026
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发表时间：
2019-04-01
影响因子：
2.2
通讯作者：
Ohdan, Hideki
中科院分区：
文献类型：
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作者：
Iwako, Hiroshi;Tashiro, Hirotaka;Ohdan, Hideki
背景：抗凝血酶（AT）不仅是止血的主要调节剂，而且还显示出抗炎特性。我们的目的是调查是否AT-不足的小鼠增加易感性肝tumorogenesis.Methods：我们诱导的AT-不足（AT（+/-））小鼠和野生型（AT（+/+））小鼠肝肿瘤的发展，通过治疗他们与二乙基亚硝胺（DEN）和四氯化碳。比较这些小鼠组之间肝肿瘤和肝脏炎症的发展。结果：与野生型小鼠相比，DEN和CCl 4诱导的AT缺陷小鼠的肿瘤体积和肿瘤数量明显增加。AT（+/-）组血清转氨酶水平、细胞死亡和肝脏中切割的caspase-3表达增加。此外，肝中性粒细胞浸润和血清白细胞介素6和肿瘤坏死因子-α水平显着升高AT不足的小鼠。AT不足小鼠肝脏DNA氧化损伤标志物8-OHdG水平显著升高。AT的管理导致显着减少DEN和四氯化碳诱导的肝损伤和炎症AT不足的小鼠，与野生型group.Conclusions相比：AT不足导致增加肝脏炎症增加对肝脏肿瘤发生的易感性。(C)2018爱思唯尔公司All rights reserved.
Background: Antithrombin (AT) is not only a major regulator of hemostasis, but it shows anti-inflammatory properties as well. We aimed to investigate whether AT-insufficient mice increase susceptibility to liver tumorigenesis.Methods: We induced the development of liver tumor in AT-insufficient (AT(+/-)) mice and wild-type (AT(+/+)) mice by treating them with diethylnitrosamine (DEN) and CCl4. The development of liver tumors and liver inflammation were compared between these mouse groups. Following this, AT was administered to the AT-insufficient mice treated with DEN and CCl4.Results: Tumor size and the number of DEN and CCl4 -induced liver tumors significantly increased in AT-insufficient mice compared with the wild-type mice. Serum transaminase levels, cell death, and the expression of cleaved caspase-3 in liver were increased in AT(+/-). Furthermore, hepatic neutrophil infiltrations and serum interleukin 6 and tumor necrosis factor-alpha levels were significantly elevated in AT-insufficient mice. The levels of 8-OHdG, oxidative DNA damage marker, in liver were significantly increased in AT-insufficient mice. Administration of AT led to a significant decrease in DEN- and CCl4 -induced liver injury and inflammation in AT-insufficient mice, compared with the wild-type group.Conclusions: AT insufficiency led to increased susceptibility to liver tumorigenesis by increasing hepatic inflammation. (C) 2018 Elsevier Inc. All rights reserved.