孕中期大鼠丙泊酚麻醉下手术对子代认知功能及海马HDAC2-CREB-NR2B信号通路的影响  

Effect of surgery under propofol anesthesia during mid-pregnancy on cognitive function and hippocampal HDAC2-CREB-NR2B signaling pathway in offspring rats

作　　者：冯运林 王胜强 冯娜敏 赵伟红[4] 罗佛全 Feng Yunlin;Wang Shengqiang;Feng Namin;Zhao Weihong;Luo Foquan(Department of Anesthesiology,the Affiliated Hospital of Guizhou Medical University,Guiyang,550000,China;Department of Anesthesiology,Yichun People′s Hospital,Yichun 336000,China;Department of Anesthesiology,the First Affiliated Hospital of Xi′an Jiaotong University,Xi′an 710000,China;Department of Anesthesiology,the First Affiliated Hospital of Nanchang University,Nanchang 330000,China;Department of Anesthesiology,Zhejiang Provincial People′s Hospital,the Affiliated People′s Hospital of Hangzhou Medcial College,Hangzhou 310000,China)

机构地区：[1]贵州医科大学附属医院麻醉科,贵阳550000 [2]宜春市人民医院麻醉科,宜春336000 [3]西安交通大学第一附属医院麻醉科,西安710000 [4]南昌大学第一附属医院麻醉科,南昌330000 [5]浙江省人民医院/杭州医学院附属人民医院麻醉科,杭州310000

出　　处：《中华麻醉学杂志》2023年第3期302-306,共5页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金(81060093,81960211)。

摘　　要：目的评价孕中期大鼠丙泊酚麻醉下手术对子代认知功能及海马组蛋白去乙酰化酶2(HDAC2)-环腺苷酸效应元件结合蛋白(CREB)-含2B亚基的N-甲基-D-天冬氨酸受体(NR2B)信号通路的影响。方法孕14 d健康SD大鼠30只,采用随机数字表法分为3组(n=10):丙泊酚组(P组)、丙泊酚手术组(S组)和对照组(C组)。S组经尾静脉注射20 mg/kg丙泊酚,继之以20 mg·kg^(-1)·h^(-1)速率连续输注维持麻醉4 h并行剖腹探查术。P组除不行剖腹探查术外,余处理同S组;C组输注等量生理盐水。子鼠出生后30 d,采用Morris水迷宫实验评价子代大鼠学习记忆能力。采用Western blot法检测子代海马组蛋白去乙酰化酶2(HDAC2)、磷酸化(p-)CREB、NR2B、脑源性神经营养因子(BDNF)和p-酪氨酸激酶B(p-TrkB)表达,TUNEL染色法检测海马神经元凋亡水平。结果与C组比较,P组和S组逃避潜伏期延长,穿越原平台位置次数减少,第二象限停留时间缩短,海马HDAC2表达上调,p-CREB、NR2B、BDNF和p-TrkB表达下调,神经元凋亡率增加(P<0.05);与P组比较,S组逃避潜伏期延长,穿越原平台位置次数减少,第二象限停留时间缩短,海马HDAC2表达上调,p-CREB、NR2B、BDNF和p-TrkB表达下调,神经元凋亡率增加(P<0.05)。结论孕中期大鼠丙泊酚麻醉下手术可降低子代认知功能,其机制与调控HDAC2-CREB-NR2B信号通路,促进海马神经元凋亡有关。Objective To evaluate the effect of surgery under propofol anesthesia during mid-pregnancy on the cognitive function and hippocampal histone deacetylase 2(HDAC2)-cAMP response element-binding protein(CREB)-N-methyl-D-aspartate(NMDA)receptor 2B subunit(NR2B)-containing NMDA receptor(NR2B)signaling pathway in the offspring rats.Methods Thirty healthy Sprague-Dawley rats at 14 days of gestation were divided into 3 groups(n=10 each)using a random number table method:propofol anesthesia group(P group),surgery under propofol anesthesia group(S group)and control group(C group).In S group,propofol 20 mg/kg was injected via the caudal vein,and then propofol was continuously infused at a rate of 20 mg·kg^(-1)·h^(-1) to maintain anesthesia for 4 h,and exploratory laparotomy was performed.Group P received no exploratory laparotomy and the other treatments were similar to those previously described in group S.The equal volume of normal saline was given instead in group C.The learning and memory of the offspring rats was assessed using Morris water maze test on postnatal day 30.The expression of HDAC2,phosphorylated CREB(p-CREB),NR2B,brain-derived neurotriphic factor(BDNF)and phosphorylated tyrosine kinase B(p-TrkB)in offspring′s hippocampi was evaluated by Western blot.Apoptosis in hippocampal neurons was detected by TUNEL staining.Results Compared with group C,the escape latency was significantly prolonged,the frequency of crossing the original platform was decreased,the time spent in the second quadrant was shortened,the expression of HDAC2 was up-regulated,the expression of p-CREB,NR2B,BDNF and p-TrkB was down-regulated,and the apoptosis rate of the hippocampal neurons was increased in P and S groups(P<0.05).Compared with P group,the escape latency was significantly prolonged,the frequency of crossing the original platform was decreased,the time spent in the second quadrant was shortened,the expression of HDAC2 was up-regulated,the expression of p-CREB,NR2B,BDNF and p-TrkB was down-regulated,and the apoptosis rate of t

关 键 词：妊娠 二异丙酚 麻醉 外科手术 认知 海马 组蛋白脱乙酰基酶2 CAMP反应元件结合蛋白质 受体 N-甲基-D-天冬氨酸 子代 

分 类 号：R614[医药卫生—麻醉学]