Effect of nerve cell apoptosis induced by endoplasmic reticulum stress on brain injury after asphyxiating cardiac arrest and resuscitation in rats

Abstract

Objective To investigate the effect of nerve cells apoptosis induced by endoplasmic reticulum stress (ERS) on brain injury after asphyxiating cardiac arrest and cardiopulmonary resuscitation (CA/CPR) in rats. Methods A total of 40 male Sprague-Dawley rats were randomly divided into control group and CA/CPR group (n=20). The CA/CPR models were established by asphyxia method/CPR. The levels of neuron specific enolization enzyme (NSE) and S100 beta protein (S100β protein) in serum at baseline and 0, 3 and 6 h after CPR were detected by double antibody sandwich enzyme-linked immunosorbent assay (ELISA). The mRNA expressions of CCAAT-enhancer binding protein homologous protein (CHOP), activate transcription factor 4 (ATF4) and X-4 box binding protein 1 (XBP1) in the hippocampus were detected by reverse transcription-polymerase chain reaction (RT-PCR). The protein expressions of CHOP, B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (caspase-3) in the hippocampus were measured by Western boltting. Neuronal apoptosis were detected by terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL). Morphological and ultrastructural changes of the hippocampi were observed by light microscopy and electron microscopy. Results As compared to that in the control group, S100β protein in the CA/CPR group at 0, 3 and 6 h after resuscitation was statistically different (P<0.05); NSE protein level in the CA/CPR group at 6 h after resuscitation was significantly higher than that in the control group (P<0.05). As compared with those in the control group, the mRNA expressions of CHOP, ATF4 and XBP-1 in the hippocampus of the CA/CPR group were obviously increased (P<0.05). Significantly increased protein expressions of CHOP, Bax, and caspase-3, and statistically decreased Bcl-2 expression in the CA/CPR group were noted as compared with those in the control group (P<0.05). The neuronal apoptosis rate in the CA/CPR group (29.74%±6.26%) was significantly higher than that in the control group (7.48%±4.34%, P<0.05). The morphology changes and ultramicrostructure injuries of the hippocampus in the CA/CPR group were more obvious as compared with those in the control group. Conclusion CA/CPR in rats causes significant damage to brain tissues, and brain injury is aggravated gradually along with the prolongation of time, and the mechanism of brain injury may be connected with ERS-induced apoptosis of nerve cells. Key words: Cardiac arrest; Cardiopulmonary resuscitation; Brain injury; Apoptosis; Endoplasmic reticulum stress