摘要目的 评价右美托咪定对猪心脏停搏复苏后脑损伤时受体相互作用蛋白1(RIP1)信号通路的影响.方法 健康雄性白猪21头,体重33～41 kg,采用随机数字表法分为3组(n=7):假手术组(S组)、心脏停搏复苏组(CA-R组)和右美托咪定组(D组).采用电刺激法诱发室颤8 min,心肺复苏5 min,制备心脏停搏复苏猪脑损伤模型.于复苏成功后5 min时,D组经股静脉输注右美托咪定负荷剂量0.5 μg/kg,随后以0.5 μg·kg-1·h-1的速率维持6 h;S组和CA-R组给予等容量生理盐水.于复苏后1、3、6和24 h(T1-4)时采用ELISA法检测血清神经元特异性烯醇化酶(NSE)和S-100β蛋白的浓度.于T4时行神经功能缺陷评分(NDS).于T4时处死动物,取大脑皮层组织,采用Western blot法检测RIP1、RIP3与混合谱系激酶域样蛋白(MLKL)的表达水平.结果 与S组比较,CA-R组和D组T1-4时血清NSE和S-100β蛋白浓度升高,T4时NDS升高,大脑皮层组织RIP1、RIP3和MLKL表达上调(P＜0.05);与CA-R组比较,D组T3,4时血清NSE和S-100β蛋白浓度降低,T4时NDS降低,大脑皮层组织RIP1、RIP3和MLKL表达下调(P＜0.05).结论 右美托咪定减轻猪心脏停搏复苏后脑损伤的机制可能与抑制RIP1信号通路活化有关.

abstractsObjective 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.