Thrombomodulin administration attenuates ischemia-reperfusion injury of the remnant liver after 70% hepatectomy in rats: simulated model of small-for-size graft in living donor liver transplantation.

Abstract:

BACKGROUND:Hepatic ischemia-reperfusion injury (IRI) is a serious complication affecting liver function and postoperative course after liver transplantation. Thrombomodulin (TM) has been known to have anticoagulant and anti-inflammatory activities exerting a cytoprotective effect. We evaluated the cytoprotective effect of recombinant human soluble TM (rhsTM) on the remnant liver exposed to IRI after 70% hepatectomy in rats, which was the simulated model of small-for-size graft in living donor liver transplantation. MATERIALS AND METHODS:A Wistar rat underwent 70% hepatectomy followed by 20-minute IRI for the remnant liver. rhsTM (1 mg/kg) (TM group) or saline (control group) was intravenously administered 30 minutes before operation. RESULTS:Alanine aminotransaminase levels were more significantly decreased during the 24 hours after operation in the TM group than in control group, especially at 6 hours. Intrahepatic infiltration of macrophages/monocytes (ED-1 immunohistochemical staining) at 6 hours was significantly decreased in the TM group compared to the control group. The number of proliferating cell nuclear antigen-positive cells at 12 hours (hepatocyte proliferation) was significantly higher in the TM group than in the control group; although liver weight 7 days after operation did not differ between the two groups. Hepatocyte apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, also known as TUNEL assay) at 24 hours was more significantly diminished in the TM group than in the control group. CONCLUSION:These results suggest that rshTM attenuates hepatocyte injury through its anti-inflammatory effect, and promotes hepatocyte proliferation in the reduced-size liver exposed to hepatic IRI.

journal_name

Transplant Proc

authors

Tanemura A,Kuriyama N,Azumi Y,Ohsawa I,Kishiwada M,Mizuno S,Usui M,Sakurai H,Tabata M,Isaji S

doi

10.1016/j.transproceed.2013.11.128

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

1107-11

issue

4

eissn

0041-1345

issn

1873-2623

pii

S0041-1345(13)01342-0

journal_volume

46

pub_type

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