Effect of dexmedetomidine pretreatment on hippocampal endoplasmic reticulum stress-induced cell apoptosis after asphyxial cardiac arrest-resuscitation in rats

Objective To investigate the effect of dexmedetomidine pretreatment on hippocampal endoplasmic reticulum stress-induced cell apoptosis after asphyxial cardiac arrest-resuscitation in rats. Methods A total of 60 pathogen-free male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-300 g, were divided into 3 groups (n=20 each) by using a random number table: control group (C group), asphyxial cardiac arrest-resuscitation group (CA group) and dexmedetomidine pretreatment group (Dex group). The anaesthetized rats were intubated with a 16G tracheal catheter which was connected to a rodent ventilator for mechanical ventilation.Cardiac arrest was induced by clamping the tracheal tube at the end of the exhalation until systolic blood pressure decreased to 25 mmHg lasting for 5 min, and then resuscitation was started.At 5 min before cardiac arrest, dexmedetomidine 4.0 μg/kg was intravenously injected in group Dex, and the equal volume of normal saline was given instead in C and CA groups.Rats were sacrificed at 6 h after successful resuscitation, brain tissues were removed for determination of wet to dry weight ratio (W/D ratio), and hippocampal tissues were obtained for examination of the pathological changes (with a light microscope) and ultrastructure (with an electron microscope) and for determination of cell apoptosis (by TUNEL), expression of CCAAT/enhancer-binding protein homologous protein (CHOP) and activated transcription factors (ATF4) and X-4 box binding protein 1 (XBP1) mRNA (by real-time polymerase chain reaction) and expression of CHOP, Bcl-2, Bax and caspase-3 (by Western blot). The apoptosis rate was calculated. Results Compared with group C, W/D ratio of brain tissues was significantly increased, the apoptosis rate of hippocampal tissues was decreased, the expression of XBP-1, ATF4 and CHOP mRNA was up-regulated, the expression of CHOP, Bax and caspase-3 was up-regulated, and the expression of Bcl-2 was down-regulated in CA and Dex groups (P<0.05). Compared with group CA, W/D ratio of brain tissues was significantly decreased, the apoptosis rate of hippocampal tissues was decreased, the expression of XBP-1, ATF4 and CHOP mRNA was down-regulated, the expression of CHOP, Bax and caspase-3 was down-regulated, the expression of Bcl-2 was up-regulated (P<0.05), and the pathological changes were significantly attenuated in group Dex. Conclusion The mechanism by which dexmedetomidine pretreatment mitigates brain injury after asphyxial cardiac arrest-resuscitation may be related to inhibiting cell apoptosis induced by endoplasmic reticulum stress in rats. Key words: Dexmedetomidine; Asphyxia; Heart arrest; Resuscitation; Brain injuries; Apoptosis; Endoplasmic reticulum; Stress