Open AccessPropofol post‐conditioning alleviates hepatic ischaemia reperfusion injury via BRG 1‐mediated Nrf2/ HO ‐1 transcriptional activation in human and mice
Author(s) -
Ge Mian,
Chen Huixin,
Zhu Qianqian,
Cai Jun,
Chen Chaojin,
Yuan Dongdong,
Jin Yi,
Yao Weifeng,
Hei Ziqing
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13279
Subject(s) - oxidative stress , chemistry , reperfusion injury , heme oxygenase , propofol , pharmacology , lactate dehydrogenase , hepatocyte , heme , microbiology and biotechnology , medicine , ischemia , biochemistry , enzyme , in vitro , biology
To explore the effects of propofol post‐conditioning ( PPC ) on hepatic ischaemia/reperfusion injury ( HIRI ) and the potential mechanisms that might be involved in the interaction of Brahma‐related gene1( BRG 1) and Nuclear‐related factor 2(Nrf2). Patients were randomized into PPC ( n = 16) and non‐ PPC ( NPC )( n = 21) groups. Propofol(2 mg/kg) was infused within 10 min. of the onset of liver reperfusion during liver transplantation in the PPC group. Liver function tests, as well as Brg1, Nrf2, Heme oxygenase‐1( HO ‐1) and NADPH :quinone oxidoreductase1( NQO 1) expression levels were evaluated. CMV ‐Brg1 mice were designed to investigate the role of Brg1 overexpression during HIRI . Brg1 and Nrf2 si RNA were used to examine the relationship between Brg1 and Nrf2/ HO ‐1 pathways in propofol‐mediated effects in a human hepatocyte(L02) hypoxia/reoxygenation(H/R) model. In patients, PPC attenuated both donor liver pathological and function injury, and reducing oxidative stress markers, compared to the NPC group, 24 hrs after surgery. PPC increased liver Brg1, Nrf2, HO ‐1 and NQO 1 expression. In mice, PPC reduced HIRI by decreasing liver oxidative stress and activating Nrf2/ HO ‐1 pathway, accompanied by up‐regulation of BRG 1 expression. BRG 1 overexpression activated Nrf2/ HO ‐1 transcription in CMV ‐ BRG 1 mice during HIRI . In vitro, PPC significantly elevated expression of Nrf2, HO ‐1 and NQO 1, resulting in a reduction of cell DCFH ‐ DA and 8‐isoprostane levels and decreased lactate dehydrogenase levels, leading to an overall increase in cell viability. Moreover, the protective effects of propofol were partially abrogated in Nrf2‐knock‐down or BRG 1‐knock‐down hepatocytes. Nrf2‐knock‐down drastically reduced protein expression of HO ‐1 and NQO 1, while Brg1‐knock‐down decreased HO ‐1 expression. Propofol post‐conditioning alleviates HIRI through BRG 1‐mediated Nrf2/ HO ‐1 transcriptional activation.