Related Experiment Video
Updated: Aug 21, 2026
Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen
Published on: November 27, 2019
Increased expression of toll-like receptor 4 enhances endotoxin-induced hepatic failure in partially hepatectomized
Tsukasa Takayashiki1, Hiroyuki Yoshidome, Fumio Kimura
1Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana Chuo-ku, Chiba, 260-0856 Japan.
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.
