摘要目的:评价预输注青年大鼠血浆对老龄大鼠术后认知功能的影响及磷脂酰肌醇3-激酶/丝氨酸苏氨酸蛋白激酶(PI3K/Akt)信号通路在其中的作用。方法:SPF级健康雄性老龄SD大鼠60只，18月龄，体重550~650 g，采用随机数字表法分为4组( n＝15)：对照组(C组)、手术组(O组)、青年大鼠血浆组(P组)和PI3K抑制剂LY294002组(LY组)。P组和LY组尾静脉注射青年大鼠血浆100 μl，C组和O组尾静脉注射等容量生理盐水，2次/周，持续4周。O组、P和LY组大鼠在七氟烷麻醉下行单侧胫骨骨折内固定术。麻醉前LY组尾静脉注射PI3K抑制剂LY294002 0.3 mg/kg。术后3 d时行旷场实验评估大鼠自发活动能力，然后行Morris水迷宫实验评估大鼠认知功能。行为学测试结束后处死大鼠，分离海马组织，采用Western blot法测定磷酸化PI3K(p-PI3K)、磷酸化Akt(p-Akt)、突触蛋白、突触素Ⅰ和突触囊泡蛋白的表达水平，透射电镜下观察海马神经元超微结构并记录突触数量。 结果:4组大鼠运动速度、路程以及旷场中心停留时间比较差异无统计学意义( P>0.05)。与C组比较，O组和LY组逃避潜伏期延长，穿越原平台次数减少，海马组织p-PI3K、p-Akt、突触蛋白、突触素Ⅰ和突触囊泡蛋白的表达下调，突触数量减少( P<0.05)，P组上述指标差异无统计学意义( P>0.05)；与O组比较，P组逃避潜伏期缩短，穿越原平台次数增加，海马组织p-PI3K、p-Akt、突触蛋白、突触素Ⅰ和突触囊泡蛋白的表达上调，突触数量增加( P<0.05)，LY组上述指标差异无统计学意义( P>0.05)；与P组比较，LY组逃避潜伏期延长，穿越原平台次数减少，海马组织p-PI3K、p-Akt、突触蛋白、突触素Ⅰ和突触囊泡蛋白的表达下调，突触数量减少( P<0.05)。 结论:预输注青年大鼠血浆可改善老龄大鼠术后认知功能，其机制与激活海马PI3K/Akt信号通路，改善突触可塑性有关。

abstractsObjective:To evaluate the effect of pre-infusion of young rat plasma on postoperative cognitive function in aged rats and role of phosphatidylinositol 3 kinase/serine-threonine protein kinase (PI3K/Akt) signaling pathway.Methods:Sixty SPF healthy male Sprague-Dawley rats, aged 18 months, weighing 550-650 g, were divided into 4 groups ( n=15 each) using a random number table method: control group (group C), operation group (group O), young rat plasma group (group P) and PI3K inhibitor LY294002 group (group LY). The young rat plasma 100 μl/time was injected via the caudal vein twice a week for 4 consecutive weeks in group P and group LY, while the equal volume of normal saline was given instead in group C and group O. Rats received internal fixation for unilateral tibial fracture under sevoflurane anesthesia in O, P and LY groups.Rats received no treatment in group C. PI3K inhibitor LY294002 0.3 mg/kg was injected through the caudal vein before anesthesia in group LY.The ability of spontaneous activity was evaluated by open field test at 3 days after surgery, and then the cognitive function was assessed by Morris water maze test.The rats were sacrificed after the end of behavioral testing, and the hippocampal tissues were isolated for determination of the expression of phosphorylated PI3K (p-PI3K), phosphorylated Akt (p-Akt), synapsin, synaptophysin I and synaptic vesicle protein (by Western blot) and for microscopic examination of the ultrastructure of hippocampal neurons (with a transmission electron microscope). The number of synapses was recorded. Results:There was no significant difference in the movement speed and length and time spent in the central zone among the four groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of p-PI3K, p-Akt, synapsin, synaptophysin I and synaptic vesicle protein was down-regulated, and the number of synapses was reduced in O and LY groups ( P<0.05), and no significant change was found in the parameters mentioned above in group P ( P>0.05). Compared with group O, the escape latency was significantly shortened, the number of crossing the original platform was increased, the expression of p-PI3K, p-Akt, synapsin, synaptophysin I and synaptic vesicle protein was up-regulated, and the number of synapses was increased in group P ( P<0.05), and no significant change was found in the parameters mentioned above in group LY ( 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-PI3K, p-Akt, synapsin, synaptophysin I and synaptic vesicle protein was down-regulated, and the number of synapses was reduced in group LY ( P<0.05). Conclusion:Pre-infusion of young rat plasma can improve postoperative cognitive function in aged rats, and the mechanism is related to activation of PI3K/Akt pathway and improvement of synaptic plasticity.