Neuroprotective effects and underlying mechanism of preconditioning with MK-801 in cerebral ischemia/reperfusion injury in rats induced by cardiac arrest-cardiopulmonary resuscitation / 中国医师杂志

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 groupscontrol 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.