Dexmedetomidine attenuates endoplasmic reticulum stress and apoptosis in brain injury after asphyxiating cardiac arrest and resuscitation in rats
10.3760/cma.j.issn.1671-8925.2018.03.010
- VernacularTitle:右美托咪定可抑制大鼠窒息性心跳骤停及复苏后脑损伤内质网应激和细胞凋亡
- Author:
Fang XING
1
;
Gang XU
;
Xihua LU
;
Dongmin ZHOU
Author Information
1. 郑州大学附属肿瘤医院麻醉科
- Keywords:
Dexmedetomidine;
Brain injury;
Apoptosis;
Endoplasmic reticulum stress;
Cardiac arrest;
Cardiopulmonary resuscitation
- From:
Chinese Journal of Neuromedicine
2018;17(3):269-276
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect ofdexmedetomidine (Dex) on endoplasmic reticulum stress (ERS) and apoptosis in brain injury after asphyxiating cardiac arrest and cardiopulmonary resuscitation (CA/CPR) in rats.Methods A total of 60 clean male Sprague-Dawley rars were randomly divided into sham-operated group,CA/CPR group and Dex precondition group (n=20).Rats in the control group did not receive CA/CPR;and rats in the CA/CPR group and Dex precondition group were performed cardiac arrest induced by asphyxia,and then,CPR was performed.Dex with dose of 4.0 microgram/kg (body weight) was intravenously injected into rats in the Dex precondition group prior to 5 min of asphyxia.The same volume of saline by intravenous injection was given to rats in control group and CA/CPR group.Brain tissues were collected after the experiment,and wet to dry weight (W/D) ratio was tested.The mRNA expressions of CCAAT-enhancer binding protein homologous protein (CHOP),activation of transcription factor 4 (A TF4) 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 was detected by terminal dexynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL).Morphological and ultrastructural changes of brains of rats were observed by light microscopy and electron microscopy.Results As compared with the control group,CA/CPR group and Dex precondition group had significantly increased W/D ratio of brain tissues and mRNA expressions of XBP1,A TF4 and CHOP in the hippocampus,significantly higher protein expressions of CHOP,Bax and caspase-3,and statistically lower Bcl-2 expression (P＜0.05).As compared with the CA/CPR group,Dex precondition group had significantly decreased W/D ratio of brain tissues and mRNA expressions of XBP1,A TF4 and CHOP in the hippocampus,significantly lower protein expressions of CHOP,Bax and caspase-3,and statistically higher Bcl-2 expression (P＜0.05).TUNEL indicated that the neuronal apoptosis rate in the control group (7.49％±4.33％) was significantly lower than that in the CA/CPR group and Dex precondition group (29.73％±6.27％ and 16.82％±5.75％,P＜0.05);significant difference was noted between CA/CPR group and Dex precondition group in the neuronal apoptosis rate (P＜0.05).Changes in the morphology and ultramicrostructure injuries of brain tissues were more significant in CA/CPR group,while the changes were obviously alleviated in Dex precondition group.Conclusion Dex can alleviate brain injury after asphyxiating CA/CPR in rats,whose mechanism may be related to ERS and inhibition on apoptosis of nerve cells.
