Hypothermic oxygenated perfusion ameliorates ischemia‐reperfusion injury of fatty liver in mice via Brg1/Nrf2/HO‐1 axis

Background After cold storage (CS) and subsequent transplantation, fatty liver is more inclined to develop liver dysfunction and serious postoperative complications in contrast to healthy liver. Hypothermic oxygenated perfusion (HOPE) is a safe and efficacious system, which can repair fatty liver and reduce ischemia‐reperfusion injury. The aim of this research is to investigate the function of Brg1/Nrf2/HO‐1 signaling pathway in the protective effect of HOPE on ischemia‐reperfusion injury of fatty liver. Methods The mouse fatty liver model was successfully established and verified by hematoxylin‐eosin (HE) staining and oil red O staining. The animals were divided into Control group, CS group and HOPE group. The levels of liver enzyme and lactate in the perfusate were used to measure liver function and cellular metabolism. HE staining and TUNEL staining were utilized to assess the tissue structure and apoptosis, respectively. The levels of superoxide dismutase, malondialdehyde and reactive oxygen species in liver tissue were measured to quantitatively analyze the degree of oxidative stress, and the expressions of protein Brg1, Nrf2 and HO‐1 were detected by means of the western blot. Double‐labeling immunofluorescence was to explore the colocalization of Brg1 and Nrf2. Results The injury of the liver in the CS group was more serious than that in the control group. However, HOPE could significantly reduce the injury, which was manifested by the improvement of liver function and cellular metabolism, and the lower degrees of apoptosis, necrosis and oxidative stress. Furthermore, the expressions of Brg1, Nrf2 and HO‐1 in the HOPE group were significantly increased than those in the CS group. Conclusions One‐hour HOPE treatment before reperfusion can obviously improve the injury of fatty liver in mice. The underlying mechanism may be that the interaction of Brg1 and Nrf2 can selectively activate the transcription of HO‐1. Fatty liver is more prone to develop ischemia‐reperfusion injury. Hypothermic oxygenated perfusion (HOPE) treatment can obviously improve the ischemia‐reperfusion injury of fatty liver. The mechanism of HOPE protection is related to Brg1/Nrf2‐mediated transcription of HO‐1 gene.