Protective effects of Salubrinal in brain death-induced liver injury

Abstract

Objective To observe the effect of salubrinal on liver cells in brain death (BD) rats and explore the relevant mechanisms. Methods Totally 40 Sprague–Dawley (SD) rats were equally randomized into four groups with random number table: sham group; BD group; salubrinal group (administered with salubrinal before BD); and DMSO group (administered with DMSO before BD). The BD models were established by increasing intracranial pressure in a modified, slow and intermittent way. In the drug groups, the drug was administered one h before the induction of BD. The mRNA expression levels of enhancer-binding protein homologous protein (CHOP) and Caspase-12 were detected by quantitative polymerase chain reaction (qPCR). The protein expression levels of P-eIF2α, CHOP, and Caspase-12 were detected by Western blotting. Apoptosis of hepatic cells was examined using the TUNEL method. Results The mRNA and protein expression levels of Chop and Caspase-12 as well as the protein expression of P-eIF2α showed no significant difference between the BD group and the DMSO group. As compared with the BD group, the P-eIF2C expression level was significantly increased in the salubrinal group after the induction of BD (P<0.05). The qPCR revealed that after the salubrinal treatment, the mRNA expression of CHOP was significantly reduced at 4th h after BD, and so did the mRNA expression of Caspase-12 (P<0.05). Western blotting indicated that the protein expression levels of Chop and Caspase-12 were also significantly decreased after salubrinal treatment. Conclusions Salubrinal can remarkably alleviate the apoptosis of hepatic cells in BD rats probably via the PERK-eIF2α signaling pathway. Key words: Rats; Liver; Brain death; Apoptosis; PKR-like edoplasmic reticulum kinase; Eukaryotic transplation initiation factor 2α