Increased expression of toll-like receptor 4 enhances endotoxin-induced hepatic failure in partially hepatectomized mice
Increased expression of toll-like receptor 4 enhances endotoxin-induced hepatic failure in partially hepatectomized mice
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DOI：
10.1016/j.jhep.2004.06.026
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发表时间：
2004-10-01
影响因子：
25.7
通讯作者：
Miyazaki, M
中科院分区：
文献类型：
--
作者：
Takayashiki, T;Yoshidome, H;Miyazaki, M
背景/目的：肝切除术后感染相关的肝衰竭仍然是死亡的原因。最近有报道，Toll样受体4（TLR 4）参与识别脂多糖（LPS）。本研究的目的是探讨TLR 4在内毒素诱导的肝损伤后hepatectomy.Methods的作用：C3 H/HeN和C3 H/HeJ小鼠进行70%肝切除或假手术，并给予LPS手术后48小时。检测TLR 4 mRNA表达、核因子-κ B（NF-κ B）活化、肿瘤坏死因子-α（TNF-α）和血清ALT水平、组织学检查结果和髓过氧化物酶含量。结果：肝切除术后6-72 h，肝组织TLR 4表达显著增加。在肝切除术后患有内毒素血症的小鼠中，肝脏NF-κ B活化大大增加。与假手术对照组相比，肝脏mRNA和血清TNF-α水平以及ALT水平显著升高。局灶性坏死伴中性粒细胞浸润明显，这与C3 H/HeN小鼠肝切除术后内毒素血症中髓过氧化物酶含量增加一致。这些在C3 H/HeJ小鼠中完全不存在。C3 H/HeN小鼠肝切除术后内毒素血症的生存率显著低于C3 H/HeJ小鼠。结论：肝切除术后TLR 4表达和功能上调在内毒素诱导的肝损伤中起关键作用。(C)2004年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: Liver failure associated with infections after hepatectomy remains a cause of mortality. It has recently been reported that toll-like receptor 4 (TLR4) is involved in recognizing lipopolysaccharides (LPS). The aim of this study was to investigate the role of TLR4 in endotoxin-induced liver injury after hepatectomy.Methods: C3H/HeN and C3H/HeJ mice underwent 70% hepatectomy or sham surgery, and LPS was administered 48 h after surgery. Expression of TLR4 mRNA, nuclear factor-kappaB (NF-kappaB) activation, tumor necrosis factor-alpha (TNF-alpha) and serum ALT levels, histological findings, and myeloperoxidase content were examined. Survival after LPS administration was also determined.Results: Hepatic expression of TLR4 was significantly increased 6-72 h after hepatectomy. In mice with endotoxemia after hepatectomy, hepatic NF-kappaB activation was greatly increased. Hepatic mRNA and serum levels of TNF-alpha, and ALT levels were significantly elevated compared with sham operated controls. Focal necrosis with neutrophil infiltration was apparent, which is consistent with increased myeloperoxidase contents in endotoxemia after hepatectomy in C3H/HeN mice. These were completely absent in C3H/HeJ mice. Survival of C3H/HeN mice with endotoxemia after hepatectomy was significantly lower than that of C3H/HeJ mice.Conclusions: Upregulated TLR4 expression and function after hepatectomy plays a pivotal role in endotoxin-induced liver injury after hepatectomy. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.