右美托咪定对幼鼠海马组织NR2B表达及学习记忆能力的影响  

Effects of dexmedetomidine on the expression of NR2B in hippocampus of young rats and the ability of learning and memory

作　　者：王玥[1] 黄晓佩[2] 鲁海兵 邱永升[1] 何秋娟 贾英萍 Wang Yue;Huang Xiaopei;Lu Haibing;Qiu Yongsheng;He Qiujuan;Jia Yingping(Department of Anesthesia and Perioperative Medicine,Children’s Hospital Affiliated to Zhengzhou University,Henan Children’s Hospital,Zhengzhou Children’s Hospital,Zhengzhou 450018,China;Department of Critical Care Medicine,Henan Provincial People’s Hospital,Zhengzhou 450000,China)

机构地区：[1]郑州大学附属儿童医院,河南省儿童医院,郑州儿童医院麻醉与围术期医学科,450018 [2]河南省人民医院重症医学科,郑州450000

出　　处：《中华实验外科杂志》2020年第9期1618-1621,共4页Chinese Journal of Experimental Surgery

基　　金：2018年河南省医学科技攻关计划(2018020696、2018020653)。

摘　　要：目的观察右美托咪定对幼鼠海马组织NR2B表达及学习记忆能力的影响。方法将80只购自河南实验动物中心的无特定病原体(SPF)级新生SD幼鼠随机分为假手术组、右美托咪定低剂量组、右美托咪定中剂量组、右美托咪定高剂量组,右美托咪定低剂量组、右美托咪定中剂量组和右美托咪定高剂量组幼鼠分别尾静脉注射20、50、100μg/kg的右美托咪定,假手术组幼鼠尾静脉注射等体积的生理盐水,连续给药3 d。采用反转录-聚合酶链反应(RT-PCR)和蛋白质印迹法(Western blot)检测海马组织NR2B mRNA和蛋白表达水平;原位缺口末端标记法(TUNEL)染色检测海马组织神经元凋亡;采用Morris水迷宫检测幼鼠学习记忆能力。组间比较采用t检验和χ2检验。结果与假手术组(2.26±0.21)比较,右美托咪定低剂量组(1.87±0.15)、右美托咪定中剂量组(1.22±0.12)、右美托咪定高剂量组(0.45±0.05)幼鼠NR2B mRNA的表达呈剂量依赖性下降(t=2.455、5.892、9.713,P<0.05)。假手术组、右美托咪定低剂量组、右美托咪定中剂量组、右美托咪定高剂量组幼鼠NR2B蛋白表达水平分别为1.88±0.16、1.46±0.14、0.91±0.09、0.34±0.02;磷酸化NR2B蛋白表达水平分别为1.31±0.11、1.01±0.09、0.63±0.06、0.22±0.03。与假手术组比较,右美托咪定低剂量组、右美托咪定中剂量组、右美托咪定高剂量组NR2B(t=2.883、6.214、9.856,P<0.05)和磷酸化NR2B(t=2.309、5.758、8.776,P<0.05)的蛋白表达呈剂量依赖性下降。假手术组、右美托咪定低剂量组、右美托咪定中剂量组、右美托咪定高剂量组幼鼠海马组织神经元凋亡数目分别为(37.66±4.11)、(35.18±3.78)、(43.33±4.05)、(59.88±5.42)个。与假手术组比较,右美托咪定高剂量组幼鼠海马组织神经元凋亡数目明显上升(t=5.255,P<0.05)。右美托咪定给药14 d后,与假手术组比较,右美托咪定高剂量组幼鼠逃避潜伏期延长,平台穿越次数下降(t=3.Objective To observe To explore the effect of dexmedetomidine on the expression of NR2B in hippocampus of young rats and the ability of learning and memory.Methods 80 specific pathogen free(SPF)newborn SD pups from Henan experimental animal center were randomly divided into sham operation group,dexmedetomidine low-dose group,dexmedetomidine middle-dose group,and dexmedetomidine high-dose group.Dexmedetomidine low-dose group,dexmedetomidine middle-dose group and dexmedetomidine high-dose group were injected with dexmedetomidine 20,50,100μg/kg through tail vein,respectively,and the sham operation group was injected with an equal volume of normal saline through the tail vein for 3 days.Reverse transcriptase-polymerase chain reaction(RT-PCR)and Western blotting were used to detect the expression of NR2B mRNA and protein in hippocampus.Terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL)staining was used to detect the neuronal apoptosis.Morris water maze was used to test the learning and memory ability.The expression of GATA4 in myocardial tissue was detected by immunohistochemistry.Enzyme linked immunosorbent assay(ELISA)was used to detect the expression of Tumor necrosis factor-α(TNF-α),interleukin(IL)-1βand IL-6 in myocardial tissue.GATA4 overexpression stable cell line was constructed,and GATA4 mRNA expression was analyzed.Results Compared with sham operation group(2.26±0.21),the mRNA expression of NR2B in low-dose dexmedetomidine group(1.87±0.15),middle-dose dexmedetomidine group(1.22±0.12),and high-dose dexmedetomidine group(0.45±0.05)decreased in a dose-dependent manner(t=2.455,5.892,9.713,P<0.05).The protein expression of NR2B in sham operation group,dexmedetomidine low-dose group,dexmedetomidine middle-dose group,and dexmedetomidine high-dose group were 1.88±0.16,1.46±0.14,0.91±0.09 and 0.34±0.02,respectively,and the protein expression of phospho-NR2B were 1.31±0.11,1.01±0.09,0.63±0.06,0.22±0.03,respectively.Compared with sham operation group,the protein expression of NR2B(t

关 键 词：NR2B 右美托咪定 凋亡 记忆能力 

分 类 号：R614[医药卫生—麻醉学]