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Volume 41 Issue 7
Jul.  2025
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Article Navigation >  Journal of Clinical Hepatology  > 2025  >  41(7): 1394-1400

Protective effect of high-altitude hypoxia acclimatization against hepatic ischemia-reperfusion injury in rats： A study based on the adenosine monophosphate-activated protein kinase/Unc-51 like autophagy activating kinase 1 signaling pathway

DOI: 10.12449/JCH250725
  • 1.

    Department of Hepatopancreatobiliary Surgery，School of Clinical Medicine，Southwest Medical University，Luzhou，Sichuan 646000，China

  • 2.

    Department of General Surgery，The General Hospital of Western Theater Command，Chengdu 610000，China

Research funding:

The Management Project of General Hospital of Western Theater Command of PLA (2021-XZYG-A12);

Sichuan Provincial Natural Science Foundation Project (41C4137G)

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  • Corresponding author: WANG Tao， watopo@163.com （ORCID： 0000-0003-4064-8867）
  • Received Date: 2024-12-01
  • Accepted Date: 2025-01-20
  • Published Date: 2025-07-25
    Abstract
  •   Objective  To investigate the protective effect of high-altitude hypoxia acclimatization against hepatic ischemia-reperfusion injury （HIRI） in rats， as well as the mechanism of action of high-altitude hypoxia acclimatization in activating autophagy.  Methods  A total of 56 male Sprague-Dawley rats were randomly divided into plain sham-operation group （P-S group）， plain model group （P-M group）， acute high-altitude hypoxia sham-operation group （AHH-S group）， acute high-altitude hypoxia model group （AHH-M group）， high-altitude hypoxia acclimatization sham-operation group （HHA-S group）， high-altitude hypoxia acclimatization model group （HHA-M group）， and high-altitude hypoxia acclimatization model group with the adenosine monophosphate-activated protein kinase （AMPK） inhibitor compound C （HHA-M-CC group）， with 8 rats in each group. The rats in the acute high-altitude hypoxia groups and the high-altitude hypoxia acclimatization groups were placed in a low-pressure oxygen chamber at an altitude of 5 000 meters for 1 week and 12 weeks， respectively； the rats in the sham-operation groups were given laparotomy to expose the portal vein without vascular clamping； the rats in the HHA-M-CC group were given abdominal injection of 20 mg/kg CC at 1 hour before surgery， while those in the other groups were given injection of an equal volume of normal saline. An automatic biochemical analyzer was used to measure the levels of liver function parameters including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and total bilirubin （TBil）； HE staining was used to observe liver histopathological changes； transmission electron microscopy was used to observe the formation of autophagosomes in liver tissue； RT-qPCR was used to measure the mRNA expression levels of AMPK and Unc-51 like autophagy activating kinase 1 （ULK1） in liver tissue； Western Blot was used to measure the protein expression levels of phosphorylated AMPK （p-AMPK）， phosphorylated ULK1 （p-ULK1）， Beclin-1， and microtubule-associated protein 1 light chain 3 Ⅱ （LC3Ⅱ）. An analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was sued for comparison between two groups.  Results  Compared with the AHH-M and HHA-M-CC groups， the HHA-M group had significantly reductions in the levels of ALT， AST， and TBil （all P<0.05）， alleviation of liver histopathological injury， a significant reduction in Suzuki score （all P<0.05）， a reduction in the degree of abnormal morphological structure of hepatocytes under transmission electron microscopy， and significant increases in the number of autophagosomes， the mRNA expression levels of AMPK and ULK1 （all P<0.05）， and the protein expression levels of p-AMPK， p-ULK1， Beclin-1， and LC3Ⅱ （all P<0.05）.  Conclusion  High-altitude hypoxia acclimatization can alleviate HIRI in SD rats by activating the AMPK/ULK1 signaling pathway and enhancing autophagy in hepatocytes.

     

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