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1 : (2017) Basic& ClinicalMedicine March2017 Vol.37 No.3 短篇综述!"#$%&'#,, ( () *+,-) *+,-)./(,* ) :!"#0 1, '# &67 89:; 5 <- Koliker Fuse=(KF=)>?& CDE G FGH IJK:L(GIRK)MNO :L>0!&89PQRSTU'#!: "#$% :R &' :A Researchprogresinmechanismsofopioids inducedrespiratorydepresion LIUXiao wen,liuzhen,zhaojing (Dept.ofAnesthesiology,PekingUnionMedicalColegeHospital,CAMS&PUMC,Beijing100730,China) Abstract:Respiratorydepresionisacommonadverseefectofopioids.Curently,themechanismsandmanage mentofopioid inducedrespiratorydepresion(oird)areoneoftheresearchfoci.oirdarisesfromstimulationof μ opioidreceptorsinthepre BotzingercomplexandtheKoliker Fuseneurons.Adenylylcyclase,calcium chan nels,andg protein gatedinwardlyrectifyingpotasium(girk)channelsmaybethekeycelularsignalingmecha nismsofoird. Keywords:opioids;opioidreceptors;respiratorydepresion 0./NVWXY 1%& W,!"# -Z[> \ #] ^_ % `a %bc!"# B 0 5% ~2% [1],89! -, 6!, Uc E,]!"#&'#, %,!"#N 69& [1 2]!"#$%& '# 1 (")*+! 0 &^ AB -! &, A B & [3]! (ventral respiratorygroup,vrg)0! &69, < 5 <(pre Botzingercom plex)mn - >, 5 < 0! & ( KF = =- >)- <= / =! (RTN/pFRG) VRG,! [3], ph&! [4] : : (correspondingauthor):zhaojing1009@aliyun.com

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4 !"#$%&'# K 5 < KF=N'b=> & μ@ < #0 AB!"#&69'#; QG, 89:;CDE GIRK: LMNO :L>!! $% 7?!& 5 6I7 R 89 # μ1@< I!"#& W AB, 455 %, &, 89!"#&FG"(: GAL CX717>) ; %!"#&23 &: [1]DahanA,AartsL,SmithTW.Incidence,reversal,and preventionofopioid inducedrespiratorydepresion[j]. Anesthesiology,2010,112: [2]GolderFJ,DaxS,BabySM,etal.Identificationandchar acterizationofgal 021asanovelbreathingcontrolmodu lator[j].anesthesiology,2015,123: [3]SmithJC,AbdalaAP,BorgmannA,etal.Brainstem re spiratorynetworks:buildingblocksandmicrocircuits[j]. TrendsNeurosci,2013,36: [4]GuyenetPG.Regulationofbreathingandautonomicout flowsbychemoreceptors[j].comprphysiol,2014,4: [5]ProftJ,WeisN.Gproteinregulationofneuronalcalcium channels:backtothefuture[j].molpharmacol,2015, 87: [6]YoungAP,GruberRB,DiscalaJF,etal.Co activationof mu anddelta opioidreceptorselicitstolerancetomorphine inducedventilatorydepresionviagenerationofperoxynitrite [J].RespirPhysiolNeurobiol,2013,186: [7]LiuX,ZouY,ZhaoJ,etal.Emergencyscenariooffenta nylinducedfaciocervicalrigidityandcompleteupperairway obstructionduringanesthesiainduction[j].chinmedj (Engl),2014,127: [8]MontandonG,QinW,LiuH,etal.PreBotzingercomplex neurokinin 1receptor expresingneuronsmediateopioid in ducedrespiratorydepresion[j].jneurosci,2011,31: [9]QiJ,LiH,ZhaoTB,etal.Inhibitoryefectofendomor phin 2bindingtothemu opioidreceptorintheratpre Botzingercomplexonthebreathingactivity[J].MolNeuro biol,2017,54: [10]ZhangZ,ZhangC,ZhuangJ,etal.Contributionofcen tralmu receptorstoswitchingpulmonaryc fibers mediated rapidshalowbreathingintoanapneabyfentanylinanes thetizedrats[j].brainres,2012,1469: [11]LevitES,AbdalaAP,PatonJF,etal.Muopioidrecep toractivationhyperpolarizesrespiratory controlingkolik er Fuseneuronsandsuppresespost inspiratorydrive[j]. JPhysiol,2015,593: [12]ZhangZ,ZhangC,ZhouM,etal.Activationofopioid mu receptors,butnotdelta orkappa receptors,switches pulmonaryc fiber mediatedrapidshalowbreathingintoan apneainanesthetizedrats[j].respirphysiolneurobiol, 2012,183: [13]SesenaE,VegaR,SotoE.Activationofmu opioidrecep torsinhibitscalcium curentsin thevestibularaferent neuronsoftheratthroughacampdependentmechanism [J].FrontCelNeurosci,2014,8:90.doi: /fn cel. [14]ManzkeT,GuentherU,PonimaskinEG,etal.5 HT4 (a)receptorsavertopioid inducedbreathingdepresion withoutlosofanalgesia[j]. Science, 2003, 301: [15]MayfieldJ,BlednovYA,HarisRA.Behavioralandge neticevidenceforgirk channelsinthecns:rolein physiology,pathophysiology,anddrugaddiction[j].int RevNeurobiol,2015,123: [16]MontandonG,RenJ,VictoriaNC,etal.G protein gated inwardlyrectifyingpotasiumchannelsmodulaterespiratory depresionbyopioids[j].anesthesiology,2016,124: [17]Velazquez MareroC,Ortiz MirandaS,MareroHG,et al.mu opioidinhibitionofca 2+ curentsandsecretionin isolatedterminalsoftheneurohypophysisoccursviaryano dine sensitiveca 2+ stores[j].jneurosci,2014,34:

5 426 Basic&ClinicalMedicine (3) [18]ChidambaranV,MaviJ,EslingerH,etal.Asociation ofoprm1a118g variantwithriskofmorphine induced respiratorydepresionfolowingspinefusioninadolescents [J].PharmacogenomicsJ,2015,15: [19]SadhasivamS,ChidambaranV,ZhangX,etal.Opioid inducedrespiratorydepresion:abcb1transporterphar macogenetics[j]. Pharmacogenomics J, 2015, 15: [20]RamaswamyS,ChangS,MehtaV.Tapentadol theevi dencesofar[j].anaesthesia,2015,70: [21]RoozekransM,vanderSchrierR,OkkerseP,etal.Two studiesonreversalofopioid inducedrespiratorydepresion bybk channelblockergal021inhumanvolunteers[j]. Anesthesiology,2014,121: [22]RenJ,DingX,GreerJ.5 HT1AreceptoragonistBefir adolreducesfentanyl inducedrespiratorydepresion,anal gesia,andsedationinrats[j].anesthesiology,2015, 122: [23]vanderSchierR,RoozekransM,vanVelzenM,etal. Opioid inducedrespiratorydepresion:reversalbynon opioiddrugs[j].f1000primerep,2014,6:79.doi: /P6 79. 新闻点击 : PQR STUVWX 据美国 WebMD 医学新闻网 ( ) 报道, 走路是个额外燃烧脂肪的绝佳方法, 但最新研究指出, 如果你在散步时变换速度会增加更多益处这篇俄亥俄州立大学所做的最新研究发现, 相较于一直维持相同速度, 改变步行的速度能多燃烧 20% 的热量测量改变速度的代谢值是非常重要的, 因为人们不是走在跑步机上面, 不会用相同的速度走路研究人员发现, 改变速度能大量增加走路消耗的热量研究人员认为, 人们可能也低估了白天走路或运动时所燃烧掉的热量, 他们估计, 在平常走路时, 开始与停下来所消耗的热量多 8% 这些热量值常常在估算燃烧热量时未包括在内研究人员 NidhiSeethapathi 强调, 以任何速度走路会消耗掉一些能量, 但当你改变速度, 你就像踩了油门改变人的动作会让腿部需要做更多, 这个过程当然会燃烧更多能量研究结果刊登在 2015 年 9 月生物学快报 (BiologyLeters) Y Z 据美国 WebMD 医学新闻网 ( ) 报道, 研究人员认为, 工作时即使只抽 10min 去散步, 也能让长时间坐着的双腿恢复血液流动纽约市哥伦比亚大学医学中心与纽约长老会医院的血管内服务主任 WiliamGray 博士认为, 最重要的结论是持续久坐且不运动会造成微血管障碍, 这是不健康的 Gary 博士认为, 运动的直接效果似乎是能增加一氧化氮含量, 一氧化氮能诱发血管打开, 降低血液的摩擦力并让血流更顺畅密苏里州哥伦比亚的密苏里大学博士生 RobertRestaino 认为, 另一个因素是步行时肌肉的收缩有助于促进循环 Gary 指出, 我们知道血流障碍与老年人心血管状况恶化有关, 但我们不知道活动所需的年龄以及持续时间是否会影响成效然而, 这篇研究的结论是, 这些短暂步行的效果是累积的, 它对于改善长期久坐造成的损伤很重要研究结果刊登在最新一期的实验心理学 (ExperimentalPhysiology)

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