右美托咪定对妊娠期七氟烷吸入麻醉诱发仔鼠海马神经元发育损伤的影响  

Effects of dexmedetomidine on developmental damage of hippocampal neurons in offspring rats induced by sevoflurane inhalation anesthesia during pregnancy

作　　者：王宇恒[1] 吴秀[1] 李明选[1] 金允淑[1] 邢宏昶[1] 孙晓峰[1] WANG Yu-heng;WU Xiu;LI Ming-xuan;JIN Yun-shu;XING Hong-chang;SUN Xiao-feng(Department of Anesthesiology,Central Hospital Affiliated to Shenyang Medical College,Shenyang 110024,Liaoning,China)

机构地区：[1]沈阳医学院附属中心医院麻醉科

出　　处：《海南医学院学报》2019年第18期1371-1375,共5页Journal of Hainan Medical University

基　　金：2018年沈阳市科学技术计划项目(18-014-4-32);辽宁省自然科学基金(2018010806-301)~~

摘　　要：目的:探讨右美托咪定对妊娠期七氟烷吸入麻醉诱发仔鼠海马神经元发育损伤的影响及其相关机制。方法:将18只妊娠期雌性Sprague-Dawley(SD)大鼠随机分为3个实验组,正常对照组(腹腔内注射0.9%氯化钠溶液100μL)、单纯七氟烷吸入麻醉组(吸入1 MAC的七氟烷6 h并腹腔内注射0.9%氯化钠溶液100μL)、右美托咪定复合七氟烷吸入麻醉组(吸入1 MAC的七氟烷6 h并腹腔内注射右美托咪定100μL)。于出生当天各实验组按窝别随机取仔鼠,左心室穿刺取动脉血做血气分析;Western Blot检测海马神经元活化型半胱天冬酶3(cleaved-caspase-3)蛋白表达;Real-time RT-PCR检测大鼠海马神经生长相关蛋白43(GAP-43)和神经型一氧化氮合酶(nNOS)mRNA表达;Western Blot和免疫组织化学法检测GAP-43和nNOS蛋白表达。结果:与正常对照组相比,单纯七氟烷吸入麻醉组仔鼠海马神经元内cleaved-caspase-3蛋白表达显著增多。右美托咪定复合七氟烷吸入麻醉后,仔鼠海马神经元内cleaved-caspase-3蛋白表达量明显低于单纯七氟烷吸入麻醉组。与单纯七氟烷吸入麻醉组相比,右美托咪定复合七氟烷吸入麻醉后能够明显上调GAP-43和nNOS mRNA和蛋白表达。结论:右美托咪定对妊娠期七氟烷吸入麻醉诱发的仔鼠海马神经元发育损伤发挥一定的保护作用,其机制可能与上调GAP-43和nNOS mRNA和蛋白表达相关。Objective:To investigate the effects of developmental damage of hippocampal neurons in offspring rats induced by sevoflurane inhalation anesthesia during pregnancyand its related mechanisms.Methods:A total of 18pregnant female Sprague-Dawley rats were randomly divided into three experimental groups:the control group(intraperitoneal injection of 0.9%sodium chloride solution 100 mL),the sevoflurane inhalation anesthesia group(inhalation of 1 MAC sevoflurane for 6h and intraperitoneal injection of 0.9%sodium chloride solution 100 mL),and the dexmedetomidine combined with sevoflurane inhalation anesthesia group(inhalation of 1 MAC sevoflurane for 6h and intraperitoneal injection of dexmedetomidine 100 mL).On the day of birth,the offspring rats of each experimental group were randomly selected.And blood gas analysis was performed with left ventricular artery blood of each offspring.The expression of cleaved-caspase-3 in hippocampal neurons was measured by Western Blot.The mRNAexpressions of growth-associated protein-43(GAP-43)and neuronal nitric oxide synthase(nNOS)in hippocampus of offspring ratswere detectedby real-timeRT-PCR.The protein expressions of GAP-43 and nNOSweretested by immunohistochemistry and Western Blot.Results:Compared with the control group,cleaved-caspase-3 expression in hippocampal neurons of offspring rats in the sevoflurane inhalation anesthesia group increased significantly.Cleaved-caspase-3 in hippocampal neurons of offspring after dexmedetomidine combined with sevoflurane inhalation anesthesia was dramatically lower than that in the sevoflurane inhalation anesthesia group.Compared with the sevoflurane inhalation anesthesia group,dexmedetomidine combined with sevoflurane inhalation anesthesia could markedly up-regulate the mRNA and protein expressions of GAP-43 and nNOS.Conclusion:Dexmedetomidine can protect hippocampal neurons from developmental damage induced by sevoflurane inhalation anesthesia during pregnancy,which may be related to the up-regulation of the mRNAand protein expressions GAP

关 键 词：右美托咪定 七氟烷 妊娠期 仔鼠海马 GAP-43 NNOS 

分 类 号：R614[医药卫生—麻醉学]