Effect of dexmedetomidine pretreatment on hippocampal endoplasmic reticulum stress-induced cell apoptosis after asphyxial cardiac arrest-resuscitation in rats
10.3760∕cma.j.issn.0254-1416.2018.03.031
- VernacularTitle:右美托咪定预先给药对大鼠窒息性心搏骤停复苏后海马内质网应激诱导细胞凋亡的影响
- Author:
Zhen ZHANG
1
;
Xihua LU
;
Qiaorong DENG
;
Meng GAO
;
Baofeng YANG
;
Yaping CUI
;
Jia LI
Author Information
1. 450008,郑州大学附属肿瘤医院麻醉科
- Keywords:
Dexmedetomidine;
Asphyxia;
Heart arrest;
Resuscitation;
Brain injuries;
Apoptosis;
Endoplasmic reticulum;
Stress
- From:
Chinese Journal of Anesthesiology
2018;38(3):376-380
- CountryChina
- Language:Chinese
-
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.
