右美托咪定的器官保护作用及其机制
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摘要
右美托咪定是一种高选择性α_2肾上腺素能受体激动剂,其通过作用于脑干蓝斑核内的α_2肾上腺素受体,产生类似自然睡眠状态的镇静、镇痛效果。近年来,右美托咪定的器官保护作用逐渐受到人们的关注,它可以通过减少去甲肾上腺素释放,抑制炎性因子生成,减少应激所致机体损伤;减少氧化应激反应所致促炎性因子生成,保护脏器功能;作用于神经传导通路,减少细胞凋亡,发挥器官保护作用。但未来仍需对右美托咪定的器官保护作用进行更广泛的研究。
Dexmedetomidine is a highly selective α_2 adrenergic receptor agonist,which produces sedative and analgesic effect similar to natural sleep by acting on α_2 adrenergic receptors in locus coeruleus nucleus of brain stem. In recent years,the organ protection effect of dexmedetomidine has gradually attracted people's attention. It can reduce the release of norepinephrine,inhibit the production of inflammatory factors,and reduce the body damage caused by stress; reduce the generation of pro-inflammatory factors caused by oxidative stress,protect the function of organs; act on nerve conduction pathway,reduce cell apoptosis,playing the role of organ protection. However,more extensive studies on the organ protection of dexmedetomidine are still needed in the future.
Dexmedetomidine is a highly selective α_2 adrenergic receptor agonist,which produces sedative and analgesic effect similar to natural sleep by acting on α_2 adrenergic receptors in locus coeruleus nucleus of brain stem. In recent years,the organ protection effect of dexmedetomidine has gradually attracted people's attention. It can reduce the release of norepinephrine,inhibit the production of inflammatory factors,and reduce the body damage caused by stress; reduce the generation of pro-inflammatory factors caused by oxidative stress,protect the function of organs; act on nerve conduction pathway,reduce cell apoptosis,playing the role of organ protection. However,more extensive studies on the organ protection of dexmedetomidine are still needed in the future.
引文
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[31]Cui J,Zhao H,Wang C,et al.Dexmedetomidine attenuates oxidative stress induced lung alveolar epithelial cell apoptosis in vitro[J].Oxid Med Cell Longev,2015,2015:358396.
[32]Zhang W,Zhang JQ,Meng FM,et al.Dexmedetomidine protects against lung ischemia-reperfusion injury by the PI3K/Akt/HIF-1αsignaling pathway[J].J Anesth,2016,30(5):826-833.
[33]Paparella D,Yau TM,Young E.Cardiopulmonary bypass induced inflammation:Pathophysiology and treatment.An update[J].Eur J Cardiothorac Surg,2002,21(2):232-244.
[34]Cho JS,Shim JK,Soh S,et al.Perioperative dexmedetomidine reduces the incidence and severity of acute kidney injury following valvular heart surgery[J].Kidney Int,2016,89(3):693-700.
[35]Zhai M,Kang F,Han M,et al.The effect of dexmedetomidine on renal function in patients undergoing cardiac valve replacement under cardiopulmonary bypass:A double-blind randomized controlled trial[J].J Clin Anesth,2017,40:33-38.
[36]Gu J,Sun P,Zhao H,et al.Dexmedetomidine provides renoprotection against ischemia-reperfusion injury in mice[J].Crit Care,2011,15(3):R153.
[37]Erk l 9,Ezgi,Kesimci E,Alaybeyoglu F,et al.Does remifentanil attenuate renal ischemia-reperfusion injury better than dexmedetomidine in rat kidney?[J].Drug Des Devel Ther,2017,11:677-683.
[2]Mei B,Meng G,Xu G,et al.Intraoperative sedation with dexmedetomidine is superior to propofol for elderly patients undergoing hip arthroplasty:A prospective randomized controlled study[J].Clin J Pain,2018,34(9):811-817.
[3]Wang WX,Wu Q,Liang SS,et al.Dexmedetomidine promotes the recovery of neurogenesis in aged mouse with postoperative cognitive dysfunction[J].Neurosci Lett,2018,677:110-116.
[4]Su X,Meng ZT,Wu XH,et al.Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery:A randomised,double-blind,placebo-controlled trial[J].Lancet,2016,388(10054):1893-1902.
[5]Tao G,Zhang J,Zhang L,et al.Sevoflurane induces tau phosphorylation and glycogen synthase kinase 3βactivation in young mice[J].Anesthesiology,2014,121(3):510-527.
[6]Hart JA,Glickman-Simon R.Phytomedicines for helicobacter pylori,garlic for hypertension,intraoperative acupuncture for tonsillectomy,omega-3 fatty acids for cognitive decline,qigong for COPD[J].Explore(NY),2016,12(2):141-145.
[7]Han C,Fu R,Lei W.Beneficial effects of dexmedetomidine on early postoperative cognitive dysfunction in pediatric patients with tonsillectomy[J].Exp Ther Med,2018,16(1):420-426.
[8]Wang D,Xu X,Wu YG,et al.Dexmedetomidine attenuates traumatic brain injury:Action pathway and mechanisms[J].Neural Regen Res,2018,13(5):819-826.
[9]Mitchell SJ.Lidocaine in the treatment of decompression illness:Areview of the literature[J].Undersea Hyperb Med,2001,28(3):165-174.
[10]Singh S,Chouhan RS,Bindra A,et al.Comparison of effect of dexmedetomidine and lidocaine on intracranial and systemic hemodynamic response to chest physiotherapy and tracheal suctioning in patients with severe traumatic brain injury[J].J Anesth,2018,32(4):518-523.
[11]Sun Z,Zhao T,Lv S,et al.Dexmedetomidine attenuates spinal cord ischemia-reperfusion injury through both anti-inflammation and anti-apoptosis mechanisms in rabbits[J].J Transl Med,2018,16(1):209.
[12]Freeman KA,Fullerton DA,Foley LS,et al.Spinal cord protection via alpha-2 agonist-mediated increase in glial cell-line-derived neurotrophic factor[J].J Thorac Cardiovasc Surg,2015,149(2):578-584;discussion 584-586.
[13]Jia ZM,Hao HN,Huang ML,et al.Influence of dexmedetomidine to cognitive function during recovery period for children with general anesthesia[J].Eur Rev Med Pharmacol Sci,2017,21(5):1106-1111.
[14]陈晓梅,陈广福.右美托咪定对颅内肿瘤手术患者血流动力学的影响及脑保护作用[J].临床麻醉学杂志,2015,31(1):15-17
[15]Yi C,Fu Z,Luo X.Dexmedetomidine on autophagy of hippocampal neurons in aged rats under sevoflurane anesthesia[J].Exp Ther Med,2018,16(2):837-841.
[16]Luo C,Ouyang MW,Fang YY,et al.Dexmedetomidine protects mouse brain from ischemia-reperfusion injury via inhibiting neuronal autophagy through up-regulating HIF-1α[J].Front Cell Neurosci,2017,11:197.
[17]Zhang X,Yan F,Feng J,et al.Dexmedetomidine inhibits inflammatory reaction in the hippocampus of septic rats by suppressing NF-κB pathway[J].PLo S One,2018,13(5):e0196897.
[18]李志行,吕敬雷,陈萍,等.缺血后处理局灶性脑缺血再灌注模型大鼠相关通路以及白细胞介素8的表达[J].中国组织工程研究,2015,19(49):7938-7944.
[19]Wang SL,Duan L,Xia B,et al.Dexmedetomidine preconditioning plays a neuroprotective role and suppresses TLR4/NF-κB pathways model of cerebral ischemia reperfusion[J].Biomed Pharmacother,2017,93:1337-1342.
[20]Chen XH,Chen DT,Huang XM,et al.Dexmedetomidine protects against chemical hypoxia-induced neurotoxicity in differentiated PC12 cells via inhibition of NADPH oxidase 2-mediated oxidative stress[J].Neurotox Res,2019,35(1):139-149.
[21]Liu YJ,Wang DY,Yang YJ,et al.Effects and mechanism of dexmedetomidine on neuronal cell injury induced by hypoxiaischemia[J].BMC Anesthesiol,2017,17(1):117.
[22]Lu P,Lei S,Li W,et al.Dexmedetomidine protects neural stem cells from ketamine-induced injury[J].Cell Physiol Biochem,2018,47(4):1377-1388.
[23]Chen Y,Zhang X,Zhang B,et al.Dexmedetomidine reduces the neuronal apoptosis related to cardiopulmonary bypass by inhibiting activation of the JAK2-STAT3 pathway[J].Drug Des Devel Ther,2017,11:2787-2799.
[24]Yi XL,Wang JT,Chu CQ,et al.Cardiocerebral protective effects of dexmedetomidine as anesthetic in colorectal cancer surgery[J].Eur Rev Med Pharmacol Sci,2018,22(11):3570-3576.
[25]Türktan M,GüneY,Yal n z H,et al.Comparison of the cardioprotective effects of dexmedetomidineand remifentanil in cardiac surgery[J].Turk J Med Sci,2017,47(5):1403-1409.
[26]Yang YF,Peng K,Liu H,et al.Dexmedetomidine preconditioning for myocardial protection in ischaemia-reperfusion injury in rats by downregulation of the high mobility group box 1-toll-like receptor 4-nuclear factorκB signalling pathway[J].Clin Exp Pharmacol Physiol,2017,44(3):353-361.
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[28]Riquelme JA,Westermeier F,Hall AR,et al.Dexmedetomidine protects the heart against ischemia-reperfusion injury by an endothelial e NOS/NO dependent mechanism[J].Pharmacol Res,2016,103:318-327.
[29]Huang SQ,Zhang J,Zhang XX,et al.Can dexmedetomidine improve arterial oxygenation and intrapulmonary shunt during onelung ventilation in adults undergoing thoracic surgery?A metaanalysis of randomized,placebo-controlled trials[J].Chin Med J(Engl),2017,130(14):1707-1714.
[30]Lee SH,Kim N,Lee CY,et al.Effects of dexmedetomidine on oxygenation and lung mechanics in patients with moderate chronic obstructive pulmonary disease undergoing lung cancer surgery:Arandomised double-blinded trial[J].Eur J Anaesthesiol,2016,33(4):275-282.
[31]Cui J,Zhao H,Wang C,et al.Dexmedetomidine attenuates oxidative stress induced lung alveolar epithelial cell apoptosis in vitro[J].Oxid Med Cell Longev,2015,2015:358396.
[32]Zhang W,Zhang JQ,Meng FM,et al.Dexmedetomidine protects against lung ischemia-reperfusion injury by the PI3K/Akt/HIF-1αsignaling pathway[J].J Anesth,2016,30(5):826-833.
[33]Paparella D,Yau TM,Young E.Cardiopulmonary bypass induced inflammation:Pathophysiology and treatment.An update[J].Eur J Cardiothorac Surg,2002,21(2):232-244.
[34]Cho JS,Shim JK,Soh S,et al.Perioperative dexmedetomidine reduces the incidence and severity of acute kidney injury following valvular heart surgery[J].Kidney Int,2016,89(3):693-700.
[35]Zhai M,Kang F,Han M,et al.The effect of dexmedetomidine on renal function in patients undergoing cardiac valve replacement under cardiopulmonary bypass:A double-blind randomized controlled trial[J].J Clin Anesth,2017,40:33-38.
[36]Gu J,Sun P,Zhao H,et al.Dexmedetomidine provides renoprotection against ischemia-reperfusion injury in mice[J].Crit Care,2011,15(3):R153.
[37]Erk l 9,Ezgi,Kesimci E,Alaybeyoglu F,et al.Does remifentanil attenuate renal ischemia-reperfusion injury better than dexmedetomidine in rat kidney?[J].Drug Des Devel Ther,2017,11:677-683.