Neuroprotective effects and underlying mechanism of preconditioning with MK-801 in cerebral ischemia/reperfusion injury in rats induced by cardiac arrest-cardiopulmonary resuscitation
10.3760/cma.j.issn.1008-1372.2018.04.016
- VernacularTitle:MK-801预处理对心脏骤停-心肺复苏大鼠脑缺血再灌注损伤的影响及机制
- Author:
Guofu LI
1
;
Cong KANG
;
Da MA
;
Guangxian CHEN
;
Zhongkai WU
Author Information
1. 523325,广东省东莞市儿童医院小儿神经外科
- Keywords:
Dizocilpine maleate/AD;
Ischemic preconditioning;
Brain ischemia;
Reperfusion injury/DT;
Receptors,glutamate/ME;
Interleukin-1 beta/ME;
Tumor necrosis factor-alpha/ME;
Rats
- From:
Journal of Chinese Physician
2018;20(4):538-542
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore effects of dizocilpine (MK-801) preconditioning on excitatory amino acids and inflammatory response in rats induced by cardiac arrest-cardiopulmonary resuscitation (CACPR).Methods 18 male Sprague Dawley (SD) rats were randomly divided into three groups:control group,CA group and CA + MK-801 group.To establish rat models of CA-CPR and keep samples of serum and specimens of brain tissues for following detection.The injury of neurons was observed by HE staining and expression of N-methyl-D-aspartic acid receptor (NMDAR) in brain tissues was detected by Western blot.The concentrations of interleukin 1 beta (IL-1 β) and tumor necrosis factor (TNF)-α in serum were detected by enzyme linked immunosorbent assay (ELISA).Results Neurons in CA group were disorganized,cells shrank,nuclei pyknosis,and cytoplasmic eosinophilia,accompanied by inflammatory cell infiltration.Preconditioning with MK-801 reduced the pathological damage of neuron and degree of macrophage infiltration.The relative expression of NMDAR protein in CA group were significantly higher than that in control group (907.9 ±24.9 vs 321.6 ± 18.4,P ＜0.001).Preconditioning with MK-801 significantly decreased the expression of NMDAR in CA + MK-801 group compared with that in CA group (512.4 ± 21.1 vs 907.9 ± 24.9).The CA group showed significantly increased concentrations of IL-1 β and TNF-α than that in control group (P ＜ 0.001),and this effect was abolished by preconditioning with MK-801.CA rats treated with MK-801 showed higher concentrations of IL-1 β and TNF-α than the control group.Conclusions Cardiac arrest causes pathological injury of neurons,up-regulates expression of NMDAR and aggravates inflammatory response.These results induce the apoptosis of nerve cells.Blocking glutamate receptor with MK-801 can inhibit expression of NMDAR,decrease level of cytokines,down-regulate inflammatory reaction degree therefore to protect the brain.
