Brain death induces the alteration of liver protein expression profiles in rabbits

Abstract

At present, there is no accurate method for evaluating the quality of liver transplant from a brain-dead donor. Proteomics are used to investigate the mechanisms involved in brain death-induced liver injury and to identify sensitive biomarkers. In the present study, age- and gender-matched rabbits were randomly divided into the brain death and sham groups. The sham served as the control. A brain-death model was established using an intracranial progressive pressurized method. The differentially expressed proteins extracted from the liver tissues of rabbits that were brain-dead for 6 h in the two groups were determined by two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization time of flight mass spectrometry. Although there was no obvious functional and morphological difference in 2, 4 and 6 h after brain death, results of the proteomics analysis revealed 973±34 and 987±38 protein spots in the control and brain death groups, respectively. Ten proteins exhibited a ≥2-fold alteration. The downregulated proteins were: aldehyde dehydrogenase, runt-related transcription factor 1 (RUNX1), inorganic pyrophosphatase, glutamate-cysteine ligase regulatory subunit and microsomal cytochrome B5. By contrast, the expression of dihydropyrimidinase- related protein 4, peroxiredoxin-6, 3-phosphoinositide-dependent protein kinase-1, 3-mercaptopyruvate and alcohol dehydrogenase were clearly upregulated. Immunohistochemistry and western blot analysis results revealed that the expression of RUNX1 was gradually increased in a time-dependent manner in 2, 4, and 6 h after brain death. In conclusion, alteration of the liver protein expression profile induced by brain death indicated the occurrence of complex pathological changes even if no functional or morphological difference was identified. Thus, RUNX1 may be a sensitive predict factor for evaluating the quality of brain death donated liver.