Open Access

Hypothermic machine perfusion attenuates ischemia/reperfusion injury against rat livers donated after cardiac death by activating the Keap1/Nrf2‑ARE signaling pathway

  • Authors:
    • Shuai Xue
    • Weiyang He
    • Xianpeng Zeng
    • Zimei Tang
    • Shoucheng Feng
    • Zibiao Zhong
    • Yan Xiong
    • Yanfeng Wang
    • Qifa Ye
  • View Affiliations

  • Published online on: May 23, 2018     https://doi.org/10.3892/mmr.2018.9065
  • Pages: 815-826
  • Copyright: © Xue et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.
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July-2018
Volume 18 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Copy and paste a formatted citation
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Spandidos Publications style
Xue S, He W, Zeng X, Tang Z, Feng S, Zhong Z, Xiong Y, Wang Y and Ye Q: Hypothermic machine perfusion attenuates ischemia/reperfusion injury against rat livers donated after cardiac death by activating the Keap1/Nrf2‑ARE signaling pathway. Mol Med Rep 18: 815-826, 2018
APA
Xue, S., He, W., Zeng, X., Tang, Z., Feng, S., Zhong, Z. ... Ye, Q. (2018). Hypothermic machine perfusion attenuates ischemia/reperfusion injury against rat livers donated after cardiac death by activating the Keap1/Nrf2‑ARE signaling pathway. Molecular Medicine Reports, 18, 815-826. https://doi.org/10.3892/mmr.2018.9065
MLA
Xue, S., He, W., Zeng, X., Tang, Z., Feng, S., Zhong, Z., Xiong, Y., Wang, Y., Ye, Q."Hypothermic machine perfusion attenuates ischemia/reperfusion injury against rat livers donated after cardiac death by activating the Keap1/Nrf2‑ARE signaling pathway". Molecular Medicine Reports 18.1 (2018): 815-826.
Chicago
Xue, S., He, W., Zeng, X., Tang, Z., Feng, S., Zhong, Z., Xiong, Y., Wang, Y., Ye, Q."Hypothermic machine perfusion attenuates ischemia/reperfusion injury against rat livers donated after cardiac death by activating the Keap1/Nrf2‑ARE signaling pathway". Molecular Medicine Reports 18, no. 1 (2018): 815-826. https://doi.org/10.3892/mmr.2018.9065