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2018 ; 18
(1
): 815-826
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Hypothermic machine perfusion attenuates ischemia/reperfusion injury against rat
livers donated after cardiac death by activating the Keap1/Nrf2?ARE signaling
pathway
#MMPMID29845199
Xue S
; He W
; Zeng X
; Tang Z
; Feng S
; Zhong Z
; Xiong Y
; Wang Y
; Ye Q
Mol Med Rep
2018[Jul]; 18
(1
): 815-826
PMID29845199
show ga
Hypothermic machine perfusion (HMP) has been demonstrated to be a more effective
method for preserving livers donated after circulatory death (DCD) than cold
storage (CS); however, the underlying mechanisms remain unclear. The aim of the
present study was to investigate the protective effects of HMP on rat DCD livers
and the possible role of the nuclear factor erythroid 2?related factor 2
(Nrf2)/antioxidant response element (ARE) signaling pathway. A total of 18 adult
male rats were randomly divided into three groups: Control, HMP and CS (n=6 per
group). To simulate the conditions of DCD liver transplantation, rat livers in
the CS and HMP groups were subjected to 30 min warm ischemia following cardiac
arrest and were then preserved by CS or HMP for 3 h. Subsequently, after 1 h of
isolated reperfusion, the extent of ischemia/reperfusion injury (IRI) and
cellular functions were assessed. During reperfusion, intrahepatic resistance and
bile production were measured, and the perfusion fluid was collected for liver
enzyme analysis. The liver tissues were then harvested for the assessment of
malondialdehyde (MDA) production, superoxide dismutase (SOD) activity, ATP
levels, as well as for histological analysis, immunohistochemistry and a terminal
deoxynucleotidyl transferase dUTP nick end labeling assay. Finally, the
expression levels of the components associated with the Nrf2?ARE signaling
pathway were analyzed via western blotting and reverse transcription?quantitative
polymerase chain reaction. The results of the present study revealed that,
compared with in the CS group, the HMP group exhibited higher levels of ATP, bile
production and SOD activity, and improved histological results; however, lower
levels of liver enzymes, apoptosis and MDA were detected. Additionally, the
findings of the present study also suggested that the Nrf2?ARE signaling pathway
may be activated by the steady laminar flow of HMP. In conclusion, HMP may
attenuate ischemia?reperfusion injury to rat DCD livers via activation of the
Nrf2?ARE signaling pathway.
|*Death
[MESH]
|*Perfusion
[MESH]
|*Reperfusion Injury/metabolism/pathology/prevention & control
[MESH]
|*Signal Transduction
[MESH]
|Animals
[MESH]
|Kelch-Like ECH-Associated Protein 1/*metabolism
[MESH]