右美托咪定对体外循环后围术期神经认知障碍老龄大鼠海马HPA轴和BDNF-ERK-CREB信号通路的影响

目的 评价右美托咪定对体外循环后围术期神经认知障碍老龄大鼠HPA轴和海马BDNF-ERK-CREB信号通路的影响.方法 选择老龄健康雄性Sprangue Dwaley大鼠120只,18～20月龄,体重400～550 g.采用随机数字表法将其分为4组(n=30):对照组(C组)、体外循环组(T组)、体外循环+右美托咪定组...

Effects of dexmedetomidine on hippocampal HPA axis and BDNF-ERK-CREB signaling pathway in elderly rats with perioperative neurocognitive impairment after extracorporeal circulation

Objective To evaluate the effect of dexmedetomidine on hippocampal HPA axis and BDNF-ERK-CREB signaling pathway in elderly rats with perioperative neurocognitive impairment after extracorporeal circulation.Methods A total of 120 healthy male SD rats aged 18~20 months,weighing 400~550 g,were divided into 4 groups(n=30 each)using a random number table method:control group(group C),extracorporeal circulation group(group T),extracorporeal circulation+dexmedetomidine group(group D),and extracorporeal circulation+normal saline group(group NS).Nothing was done for group C.The model of extracorporeal circulation was established in group T.After intraperitoneal injection of 50μg/kg dexmedetomidine,the model of extracorporeal circulation was established in group D.After intraperitoneal injection of 50μg/kg normal saline,the model of extracorporeal circulation was established in group NS.Morris water maze was used to determine the ability of spatial learning and memory in rats.The ability of rats to learn conditioned responses was tested using a shuttle box experiment.The open-field experiment was used to test the adaptability and cognitive ability of rats in new and different environments.The concentrations of CRH,ACTH and CORT in rat′s plasma were determined by ELISA.The expression of BDNF,ERK and CREB in the hippocampus of rats was determined by Western blot.Immunohistochemical method was used to determine the number of neurons in hippocampus BDNF,ERK and CREB.Results Compared with group C,the escape latency prolonged and the number of crossing the original platform were reduced in group T,group D and group NS;also,the number of active avoidance responses was decreased,the latency of active and passive avoidance responses was prolonged;the number of standing on the back legs of rats was decreased;the central compartment stay was longer;the concentrations of CRH,ACTH and CORT in the plasma were increased;the expression of BDNF,ERK and CREB protein and the number of positive neurons in hippocampus were decreased in group T,group D and group NS(P<0.05).Compared with group T and group NS,the escape latency was shortened and the number of crossing the original platform was increased in group D.The number of active avoidance responses was increased;the latency of active and passive avoidance responses was shortened;the number of standing on the back legs of rats was increased;the central compartment stay was shortened;the concentrations of CRH,ACTH and CORT in the plasma was decreased.The expression of BDNF,ERK and CREB protein and the number of positive neurons in hippocampus were increased in group D(P<0.05).Conclusion Dexmedetomidine can improve perioperative neurocognitive impairment in elderly rats undergoing extracorporeal circulation,and its mechanism may be related to inhibition of HPA axis and activation of BDNF-ERK-CREB signaling pathway in the hippocampus.