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

Jianbo Li; XiangJun Zha; Yan Kang; Zhongwei Zhang; Lvnan Yan; Lujia Song; Chengdi Wang; Jiayin Yang

doi:10.1016/j.isci.2022.105858

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

iScience. 2022 Dec 21;26(1):105858. doi: 10.1016/j.isci.2022.105858. eCollection 2023 Jan 20.

Authors

Jianbo Li¹, XiangJun Zha^{2

3}, Yan Kang¹, Zhongwei Zhang¹, Lvnan Yan³, Lujia Song⁴, Chengdi Wang⁴, Jiayin Yang³

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.

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.