Effect of dexmedetomidine on receptor interacting protein 1 signaling pathway during brain injury after cardiac arrest and resuscitation in pigs / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of dexmedetomidine on receptor-interacting protein 1 (RIP1) signaling pathway during brain injury after cardiac arrest and resuscitation in pigs.Methods Twenty-one healthy domestic male white pigs,weighing 33-41 kg,were divided into 3 groups (n =7 each) using a random number table method:sham operation group (group S),cardiac arrest-resuscitation group (group CA-R) and dexmedetomidine group (group D).Ventricular fibrillation was electrically induced and untreated for 8 min followed by 5 min of cardiopulmonary resuscitation to establish the model of brain injury after cardiac arrest and resuscitation in anesthetized domestic white pigs.Dexmedetomidine was infused via the femoral vein in a loading dose of 0.5 μg/kg at 5 min after successful resuscitation,followed by an infusion of 0.5 μg · kg-1 · h-1 for 6 h in group D.The equal volume of normal saline was given instead in S and CA-R groups.The concentrations of neuron-specific endase (NSE) and S-100β protein in serum were measured at 1,3,6 and 24 h after resuscitation (T1-4).Neurologic deficit score (NDS) was evaluated at T4.The animals were sacrificed at T4,brains were removed and cerebral cortex tissues were obtained for determination of the expression of RIP1,RIP3 and mixed lineage kinase domain-like protein (MLKL) by Western blot.Results Compared with group S,the serum concentrations of NSE and S-100β protein were significantly increased at T1-4,the NDS was increased at T4,and the expression of RIP1,R1P3 and MLKL in cerebral cortex tissues was up-regulated in CA-R and D groups (P＜0.05).Compared with group CA-R,the serum concentrations of NSE and S-100β protein were significantly decreased at T3,4,the NDS was decreased at T4,and the expression of RIP1,RIP3 and MLKL in cerebral cortex tissues was down-regulated in group D (P＜0.05).Conclusion The mechanism by which dexmedetomidine reduces brain injury after cardiac arrest and resuscitation may be related to inhibiting the activation of RIP 1 signaling pathway in pigs.