海马PI3K/Akt/GSK-3β信号通路在右美托咪定减轻异丙酚致新生大鼠远期认知功能减退中的作用  

Role of hippocampal PI3K/Akt/GSK-3β signaling pathway in dexmedetomidine-induced reduction of long-term cognitive decline caused by propofol in neonatal rats

作　　者：涂友兵 周丽芳[1] 韦祎 陈静[1] 谢玉波[1] Tu Youbing, Zhou Lifang, Wei Yi, Chen ring, Xie Yubo(Department of Anesthesiology, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China)

机构地区：[1]广西医科大学第一附属医院麻醉科,南宁市530021

出　　处：《中华麻醉学杂志》2018年第4期407-412,共6页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（81373498,81060277）;广西科学研究与技术开发计划项目（桂科攻1355005-4-2）;广西高校科学技术研究项目（2013ZD014）

摘　　要：目的 评价海马磷脂酰肌醇3-激酶/蛋白质丝氨酸苏氨酸激酶/糖原合成酶激酶-3β（PI3K/Akt/GSK-3β）信号通路在右美托咪定减轻异丙酚致新生大鼠远期认知功能减退中的作用.方法 清洁级健康雄性SD大鼠110只,7日龄,体重10～15 g,采用随机数字表法分为11组（n=10）：生理盐水组（NS组）、脂肪乳剂组（F组）、10％二甲基亚砜（DMSO）2组（D2组）、右美托咪定组（DEX组）和TDZD-8组（TDZD组）分别腹腔注射生理盐水、脂肪乳剂、10％DMSO 100μl、右美托咪定75μg/kg和TDZD-8 1 mg/kg;10％DMSO1组（D1组）和LY294002组（LY组）分别经侧脑室注射10％DM-SO 5μl和LY294002 25 μg/5 μl;异丙酚组（P组）腹腔注射异丙酚50 mg/kg,待翻正反射恢复后追加50 mg/kg;右美托咪定＋异丙酚组（PD组）腹腔注射右美托咪定75 μg/kg,30 min后注射异丙酚;LY294002＋右美托咪定＋异丙酚组（LYPD组）注射LY294002,30 min后注射右美托咪定,30 min后注射异丙酚;TDZD-8＋右美托咪定＋异丙酚组（TDPD组）注射TDZD-8,余处理同LYPD组.苏醒后继续饲养至9周龄.采用Morris水迷宫实验评价认知功能;随后处死大鼠取海马,采用RT-PCR法检测PI3K、Akt、GSK-3β、PSD95的mRNA表达;采用Western blot法检测Akt、pAkt（ser473）、GSK-3β、pG-SK-3β （ser9）、PSD95的表达.结果 与NS组比较,P组逃避潜伏期延长,穿越原平台次数减少,PI3K、Akt和PSD95的mRNA表达下调,GSK-3β mRNA表达上调,p-Akt（ser473）/Akt比值降低,PSD95表达下调,pGSK-3β （ser9）/GSK-3β比值升高（P＜0.05）;与P组比较,PD组、LYPD组和TDPD组逃避潜伏期缩短,穿越原平台次数增加,PD组PI3K、Akt和PSD95的mRNA表达上调,GSK-3βmRNA表达下调,PD组和TDPD组pAkt（ser473）/Akt比值升高,PSD95表达上调,pGSK-3β（ser9）/GSK-3β比值降低（P＜0.05）;与PD组比较,LYPD组逃避潜伏期延长,穿越原平台次数减少,GSK-3βmRNA表达上调,PSD95 mRNA表达下调,pAkt（ser473）/AkObjective To evaluate the role of hippocampal phosphatidylinositol 3-kinase/serinethreonine kinase/glycogen synthase kinase-3 beta （PI3K/Akt/GSK-3β） signaling pathway in dexmedetomidine-induced reduction of long-term cognitive decline caused by propofol in neonatal rats.Methods A total of 110 clean healthy male Sprague-Dawley rats,aged 7 days,weighing 10-15 g,were divided into 11 groups （n=10 each） using a random number table：normal saline group （NS group）,fat emulsion group （F group）,10% dimethyl sulfoxide （DMSO） group （D2 group）,dexmedetomidine group （DEX group）,TDZD-8 group （TDZD group）,10% DMSO group （D1 group）,LY294002 group （LY group）,propofol group （P group）,dexmedetomidine plus propofol group （PD group）,LY294002 plus dexmedetomidine plus propofol group （LYPD group） and TDZD-8 plus dexmedetomidine plus propofol group （TDPD group）.Normal saline,fat emulsion,10% DMSO 100 μl,dexmedetomidine 75 μg/kg and TDZD-8 1 mg/kg were intraperitoneally injected in NS,F,D2,DEX and TDZD groups,respectively.10% DMSO 5 μ1 and LY294002 25 μg/5 μl were injected via the lateral cerebral ventricle in D1 and LY groups,respectively.Propofol 50 mg/kg was intraperitoneally injected,and an increment of propofol 50 mg/kg was given after recovery of righting reflex in group P.Dexmedetomidine 75 μg/kg was intraperitoneally injected and 30 min later propofol was injected in group PD.LY294002 was injected,30 min later dexmedetomidine was injected,and 30 min later propofol was injected in group LYPD.In group TDPD,TDZD-8 was injected and the other treatment was similar to those previously described in group LYPD.Then the rats were fed to 9 weeks old after returning to the state of consciousness.Morris water maze test was performed to evaluate the cognitive function.Rats were then sacrificed and their hippocampi were harvested for detection of the expression of PI3K,Akt,GSK-3β and PSD95 mRNA （using real-time polymerase chain reaction） and expression of Akt,pAkt（ser473）

关 键 词：1-磷脂酰肌醇3-激酶 蛋白质丝氨酸苏氨酸激酶 糖原合成酶激酶3 右美托咪啶 二异丙酚 海马 认知障碍 婴儿 新生 

分 类 号：R614[医药卫生—麻醉学]