2. Academic Validation
  3. Oxygen-carrying sequential preservation mitigates liver grafts ischemia-reperfusion injury

Oxygen-carrying sequential preservation mitigates liver grafts ischemia-reperfusion injury

  • iScience. 2022 Dec 21;26(1):105858. doi: 10.1016/j.isci.2022.105858.
Jianbo Li 1,  XiangJun Zha 2 3,  Yan Kang 1,  Zhongwei Zhang 1,  Lvnan Yan 3,  Lujia Song 4,  Chengdi Wang 4,  Jiayin Yang 3
Affiliations

Affiliations

  • 1 Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu 610041, China.
  • 2 Department of Liver Surgery of West China Hospital and State Key Laboratory of Polymer Materials Engineering of Sichuan University, Chengdu610065, China.
  • 3 Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu610041, China.
  • 4 Department of Respiratory and Critical Care Medicine, Med-X Center for Manufacturing, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, China.
PMID: 36636350 DOI: 10.1016/j.isci.2022.105858
Abstract

Oxygen-dependent preservation has been proposed to protect liver grafts from ischemia-reperfusion injury (IRI), but its underlying mechanism remains elusive. Here, we proposed an oxygen-carrying sequential preservation (OCSP) method that combined oxygenated static cold storage (SCS) and normothermic mechanical perfusion. We demonstrated that OCSP, especially with high oxygen partial pressure level (500-650mmHg) during the oxygenated SCS phase, was associated with decreased IRI of liver grafts and improved rat survival after transplantation. A negative correlation between Autophagy and endoplasmic reticulum stress response (ERSR) was found under OCSP and functional studies indicated OCSP suppressed ERSR-mediated cell Apoptosis through Autophagy activation. Further data showed that OCSP-induced Autophagy activation and ERSR inhibition were oxygen-dependent. Finally, activated NFE2L2-HMOX1 signaling was found to induce Autophagy under OCSP. Together, our findings indicate oxygen-dependent Autophagy mitigates liver graft's IRI by ERSR suppression and modulates NFE2L2-HMOX1 signaling under OCSP, providing a theoretical basis for liver preservation using a composite-sequential mode.

Keywords

Animal physiology; Biological sciences; Physiology.

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