Effect of dexmedetomidine pretreatment on hippocampal endoplasmic reticulum stress-induced cell apoptosis after asphyxial cardiac arrest-resuscitation in rats / 中华麻醉学杂志

ABSTRACT

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), as-phyxial 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 sacri-ficed 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 ap-optosis (by TUNEL), expression of CCAAT∕enhancer-binding protein homologous protein (CHOP) and ac-tivated transcription factors (ATF4) and X-4 box binding protein 1 (XBP1) mRNA (by real-time polymer-ase 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 in-creased, 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 dexmedetomi-dine pretreatment mitigates brain injury after asphyxial cardiac arrest-resuscitation may be related to inhibi-ting cell apoptosis induced by endoplasmic reticulum stress in rats.