Effect of pre-infusion of young rat plasma on cognitive dysfunction induced by sevoflurane in aged rats and role of ERK-CREB signaling pathway / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the effect of pre-infusion of young rat plasma on cognitive dysfunction induced by sevoflurane in aged rats and the role of extracellular regulated protein kinase (ERK)-cyclic adenosine monophosphate effector binding protein (CREB) signaling pathway.Methods:One hundred and twenty SPF healthy male Wistar rats, aged 18 months, weighing 550-650 g, were divided into 4 groups ( n=30 each) using a random number table method: control group (group C), sevoflurane anesthesia group (group S), young rat plasma group (group P) and ERK inhibitor SL327 group (group SL). The teated plasma 100 μl from 3-month-old young rats was injected via the tail vein in group P and group SL, while the equal volume of normal saline was given via the tail vein in group C and group S, twice a week, for 4 weeks.In S, P and SL groups, 3% sevoflurane was inhaled for 3 h at the end of injection, and ERK inhibitor SL327 50 mg/kg was injected via the tail vein before anesthesia in group SL.The cognitive function was evaluated by Morris water maze test at 1 day before anesthesia and at 3 and 7 days after anesthesia.The rats were sacrificed, and their hippocampi were isolated for determination of the expression of phosphorylated ERK (p-ERK), p-CREB, synapsin, synapsin Ⅰ and synaptophysin and for examination of the ultrastructure of neurons (by transmission electron microscopy). The number of synapses was recorded. Results:Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of p-ERK, p-CREB, synapsin, synapsin Ⅰ and synaptophysin was down-regulated, and the number of synapses was decreased at each time point after anesthesia in the other 3 groups ( P<0.05). Compared with group S, the escape latency was significantly shortened, the number of crossing the original platform was increased, the expression of p-ERK, p-CREB, synapsin, synapsin Ⅰ and synaptophysin was up-regulated, and the number of synapses was increased at each time point after anesthesia in P and SL groups ( P<0.05). Compared with group P, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of p-ERK, p-CREB, synapsin, synapsin Ⅰ and synaptophysin was down-regulated, and the number of synapses was decreased in group SL ( P<0.05). Conclusion:Pre-infusion of young rat plasma can reduce cognitive dysfunction induced by sevoflurane in aged rats, and the mechanism is related to activation of ERK-CREB signaling pathway and improvement of synaptic plasticity.