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World J Gastroenterol. 2018 Apr 21;24(15):1622-1631. doi: 10.3748/wjg.v24.i15.1622.

Evaluation of safety for hepatectomy in a novel mouse model with nonalcoholic-steatohepatitis.

Author information

1
Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
2
Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
3
Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, Japan.
4
Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan. nokochi3@md.tsukuba.ac.jp.

Abstract

AIM:

To investigate whether the liver resection volume in a newly developed nonalcoholic steatohepatitis (NASH) model influences surgical outcome.

METHODS:

For establishment of a NASH model, mice were fed a high-fat diet for 4 wk, administered CCl4 for the last 2 wk, and administered T0901317 for the last 5 d. We divided these mice into two groups: A 30% partial hepatectomy (PH) of NASH liver group and a 70% PH of NASH liver group. In addition, a 70% PH of normal liver group served as the control. Each group was evaluated for survival rate, regeneration, apoptosis, necrosis and DNA expression after PH.

RESULTS:

In the 70% PH of NASH group, the survival rate was significantly decreased compared with that in the control and 30% PH of NASH groups (P < 0.01). 10 of 32 mice in the NASH 70% PH group died within 48 h after PH. Serum aspartate aminotransferase (AST) levels and total bilirubin (T-Bil) in the NASH 70% PH group were significantly higher than the levels in the other two groups (AST: P < 0.05, T-Bil: P < 0.01). In both PH of NASH groups, signaling proteins involved in regeneration were expressed at lower levels than those in the control group (P < 0.01). The 70% PH of NASH group also exhibited a lower number of Ki-67-positive cells and higher rates of apoptosis and necrosis than the NASH 30% PH group (P < 0.01). In addition, DNA microarray assays showed differences in gene expression associated with cell cycle arrest and apoptosis.

CONCLUSION:

The function of the residual liver is impaired in fatty liver compared to normal liver. A larger residual volume is required to maintain liver functions in mice with NASH.

KEYWORDS:

Hepatectomy; Liver proliferation; Liver regeneration; Nonalcoholic steatohepatitis; Residual liver

PMID:
29686469
PMCID:
PMC5910545
DOI:
10.3748/wjg.v24.i15.1622
[Indexed for MEDLINE]
Free PMC Article

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