PI3K/Akt/mTOR信号通路在依达拉奉减轻老龄大鼠术后认知功能障碍中的作用  

Role of PI3K/Akt/mTOR signaling pathway in edaravone-induced reduction of postoperative cognitive dysfunction in aged rats

作　　者：苏莉[1] 许亮[2] 郭涛[1] 卞立松 张澄素 王硕 Su Li;Xu Liang;Guo Tao;Bian Lisong;Zhang Chengsu;Wang Shuo(Department of Anesthesiology,Beijing Haidian Hospital,Beijing 100080,China;Department of Neurosurgery,Beijing Haidian Hospital,Beijing 100080,China)

机构地区：[1]北京市海淀医院麻醉科,北京100080 [2]北京市海淀医院神经外科,北京100080

出　　处：《中华麻醉学杂志》2023年第4期432-436,共5页Chinese Journal of Anesthesiology

摘　　要：目的评价磷脂酰肌醇3-激酶(PI3K)/丝氨酸-苏氨酸蛋白激酶(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路在依达拉奉减轻老龄大鼠术后认知功能障碍中的作用。方法健康雄性SD大鼠60只,20月龄,体质量600~700 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)、依达拉奉组(E组)和PI3K抑制剂LY294002组(LY组)。O组、E组和LY组于3%七氟烷麻醉下行剖腹探查术。E组和LY组术前30 min时腹腔注射依达拉奉3 mg/kg,同时LY组尾静脉注射LY2940020.3 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。行为学实验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)、磷酸化mTOR(p-mTOR)、突触素(SYP)和突触后致密蛋白95(PSD-95)的表达水平,行高尔基染色记录海马CA1区神经元树突长度,计算树突棘密度。结果4组运动速度、路程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组逃避潜伏期延长,穿越原平台位置次数减少,海马p-PI3K、p-Akt、p-mTOR、SYP和PSD-95表达下调,海马CA1区神经元树突长度缩短,树突棘密度降低(P<0.05);与O组比较,E组逃避潜伏期缩短,穿越原平台位置次数增加,海马p-PI3K、p-Akt、p-mTOR、SYP和PSD-95表达上调,海马CA1区神经元树突长度增加,树突棘密度升高(P<0.05);与E组比较,LY组逃避潜伏期延长,穿越原平台位置次数减少,海马p-PI3K、p-Akt、p-mTOR、SYP和PSD-95表达下调,海马CA1区神经元树突长度缩短,树突棘密度降低(P<0.05)。结论依达拉奉减轻老龄大鼠术后认知功能障碍的机制与激活PI3K/Akt/mTOR信号通路,改善海马突触可塑性有关。Objective To evaluate the role of phosphatidylinositol 3-kinase(PI3K)/serine threonine protein kinase(Akt)/mammalian rapamycin target protein(mTOR)signaling pathway in edaravone-induced reduction of postoperative cognitive dysfunction in aged rats.Methods Sixty healthy male Sprague-Dawley rats,aged 20 months,weighing 600-700 g,were divided into 4 groups(n=15 each)using a random number table method:control group(group C),operation group(group O),edaravone group(group E)and PI3K inhibitor LY294002 group(group LY).The rats received laparotomy under 3%sevoflurane anesthesia in O,E and LY groups.Edaravone 3 mg/kg was intraperitoneally injected at 30 min before operation in E and LY groups,and LY2940020.3 mg/kg was simultaneously injected via the tail vein in group LY.Open field test was performed at 3 days after surgery to evaluate the spontaneous activity of rats,then Morris water maze test was performed to evaluate the cognitive function of rats.The rats were sacrificed after the end of behavioral experiment to isolate hippocampal tissues for determination of the expression of phosphorylated PI3K(p-PI3K),phosphorylated Akt(p-Akt),phosphorylated mTOR(p-mTOR),synaptophysin(SYP)and postsynaptic density protein 95(PSD 95)(by Western blot)and dendrite length in hippocampal CA1 area(using Golgi staining).The density of dendrites was calculated.Results There were no statistically significant differences in exercise speed,distance,and time of staying at the center between 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,p-mTOR,SYP and PSD-95 was down-regulated,the dendritic length of neurons in hippocampal CA1 region was shortened,and the density of neurons in hippocampal CA1 region was decreased in group O(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,p-mTOR,SYP and PSD-95 w

关 键 词：依达拉奉 术后认知并发症 老年人 磷酸肌醇3-激酶类 蛋白质丝氨酸苏氨酸激酶 TOR丝氨酸-苏氨酸激酶 

分 类 号：R614[医药卫生—麻醉学]