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Abstract: The aim was to investigate how the PI3K/Akt pathway is involved in the protection of dexmedetomidine against propofol. The hippocampal neurons from fetal rats were separated and cultured in a neurobasal medium. Cell viability was assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Then neurons were pretreated with different concentrations of dexmedetomidine before 100 μmol/L propofol was added. Akt, phospho-Akt (p-Akt), Bad, phospho-Bad (p-Bad), and Bcl-xL were detected by Western blot. Also, neurons were pretreated with dexmedetomidine alone or given the inhibitor LY294002 before dexmedetomidine pretreatment, and then propofol was added for 3 h. The results demonstrated that propofol decreased the cell viability and the expression of p-Akt and p-Bad proteins, increased the level of Bad, and reduced the ratio of Bcl-xL/Bad. dexmedetomidine pretreatment could reverse these effects. The enhancement of p-Akt and p-Bad induced by dexmedetomidine was prevented by LY294002. These results showed that dexmedetomidine potently protected the developing neuron and this protection may be partly mediated by the PI3K/Akt pathway.

PI3K/Akt信号通路部分参与了右美托咪定对异丙酚诱导的胎鼠海马神经元凋亡的保护作用

[1]Bhana, N., Goa, K.L., McClellan, K.J., 2000. Dexmedetomidine. Drugs, 59(2):263-270.

[2]Cai, Y., Xu, H., Yan, J., et al., 2014. Molecular targets and mechanism of action of dexmedetomidine in treatment of ischemia/reperfusion injury. Mol. Med. Rep., 9(5):1542-1550.

[3]Cantley, L.C., 2002. The phosphoinositide 3-kinase pathway. Science, 296(5573):1655-1657.

[4]Cattano, D., Young, C., Straiko, M.M., et al., 2008. Subanesthetic doses of propofol induce neuroapoptosis in the infant mouse brain. Anesth. Analg., 106(6):1712-1714.

[5]Clancy, B., Darlington, R.B., Finlay, B.L., 2001. Translating developmental time across mammalian species. Neuroscience, 105(1):7-17.

[6]Creeley, C., Dikranian, K., Dissen, G., et al., 2013. Propofol-induced apoptosis of neurones and oligodendrocytes in fetal and neonatal rhesus macaque brain. Br. J. Anaesth., 110(Suppl. 1):i29-i38.

[7]Degos, V., Charpentier, T.L., Chhor, V., et al., 2013. Neuroprotective effects of dexmedetomidine against glutamate agonist-induced neuronal cell death are related to increased astrocyte brain-derived neurotrophic factor expression. Anesthesiology, 118(5):1123-1132.

[8]Duan, X., Li, Y., Zhou, C., et al., 2014. Dexmedetomidine provides neuroprotection: impact on ketamine-induced neuroapoptosis in the developing rat brain. Acta Anaesthesiol. Scand., 58(9):1121-1126.

[9]Ikonomidou, C., Bosch, F., Miksa, M., et al., 1999. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science, 283(5398):70-74.

[10]Ikonomidou, C., Bittigau, P., Ishimaru, M.J., et al., 2000. Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome. Science, 287(5455):1056-1060.

[11]Ikonomidou, C., Bittigau, P., Koch, C., et al., 2001. Neurotransmitters and apoptosis in the developing brain. Biochem. Pharmacol., 62(4):401-405.

[12]Irifune, M., Takarada, T., Shimizu, Y., et al., 2003. Propofol-induced anesthesia in mice is mediated by γ-aminobutyric acid-A and excitatory amino acid receptors. Anesth. Analg., 97(2):424-429.

[13]Jauniaux, E., Gulbis, B., Shannon, C., et al., 1998. Placental propofol transfer and fetal sedation during maternal general anaesthesia in early pregnancy. Lancet, 352(9124):290-291.

[14]Jevtovic-Todorovic, V., Hartman, R.E., Izumi, Y., et al., 2003. Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J. Neurosci., 23(3):876-882.

[15]Karen, T., Schlager, G.W., Bandix, I., et al., 2013. Effect of propofol in the immature rat brain on short- and long-term neurodevelopmental outcome. PLoS ONE, 8(5):e64480.

[16]Li, J., Xiong, M., Nadavaluru, P.R., et al., 2016. Dexmedetomidine attenuates neurotoxicity induced by prenatal propofol exposure. J. Neurosurg. Anesth., 28(1):51-64.

[17]Li, Y., Zeng, M., Chen, W., et al., 2014. Dexmedetomidine reduces isoflurane-induced neuroapoptosis partly by preserving PI3K/Akt pathway in the hippocampus of neonatal rats. PLoS ONE, 9(4):e93639.

[18]Liao, Z., Cao, D., Han, X., et al., 2014. Both JNK and P38 MAPK pathways participate in the protection by dexmedetomidine against isoflurane-induced neuroapoptosis in the hippocampus of neonatal rats. Brain Res. Bull., 107:69-78.

[19]Nguyen, H.T., Li, K.Y., daGraca, R.L., et al., 2009. Behavior and cellular evidence for propofol-induced hypnosis involving brain glycine receptors. Anesthesiology, 110(2):326-332.

[20]Ngwenyama, N.E., Anderson, J., Hoernschemeyer, D.G., et al., 2008. Effects of dexmedetomidine on propofol and remifentanil infusion rates during total intravenous anesthesia for spine surgery in adolescents. Paediatr. Anaesth., 18(12):1190-1195.

[21]Orrei, M.G., Catizone, L., Pavlica, P., et al., 1986. Radiologic surveillance of uremic osteodystrophy after parathyroidectomy. Radiol. Med., 72(7-8):521-752.

[22]Pan, W., Lin, L., Zhang, N., et al., 2016. Neuroprotective effects of dexmedetomidine against hypoxia-induced nervous system injury are related to inhibition of NF-κB/COX-2 pathways. Cell. Mol. Neurobiol., 36(7):1179-1188.

[23]Paris, A., Mantz, J., Tonner, P.H., et al., 2006. The effects of dexmedetomidine on perinatal excitotoxic brain injury are mediated by the α2A-adrenoceptor subtype. Anesth. Analg., 102(2):456-461.

[24]Pesic, V., Milanovic, D., Tanic, N., et al., 2009. Potential mechanism of cell death in the developing rat brain induced by propofol anesthesia. Int. J. Dev. Neurosci., 27(3):279-287.

[25]Ramsay, M.A., Luterman, D.L., 2004. Dexmedetomidine as a total intravenous anesthetic agent. Anesthesiology, 101(3):787-790.

[26]Sanders, R.D., Maze, M., 2007. α2-Adrenoceptor agonists. Curr. Opin. Investig. Drugs, 8(1):25-33.

[27]Sanders, R.D., Sun, P., Patel, S., et al., 2010. Dexmedetomidine provides cortical neuroprotection: impact on anaesthetic-induced neuroapoptosis in the rat developing brain. Acta Anaesthesiol. Scand., 54(6):710-716.

[28]Schoeler, M., Loetscher, P.D., Rossaint, R., et al., 2012. Dexmedetomidine is neuroprotective in an in vitro model for traumatic brain injury. BMC Neurol., 12:20.

[29]Taniguchi, T., Kidani, Y., Kanakura, H., et al., 2004. Effects of dexmedetomidine on mortality rate and inflammatory responses to endotoxin-induced shock in rats. Crit. Care Med., 32(6):1322-1326.

[30]Workman, A.D., Charvet, C.J., Clancy, B., et al., 2013. Modeling transformations of neurodevelopmental sequences across mammalian species. J. Neurosci., 33(17):7368-7383.

[31]Xiong, B., Shi, Q.Q., Miao, C.H., 2014. Dexmedetomidine renders a brain protection on hippocampal formation through inhibition of nNOS-NO signalling in endotoxin-induced shock rats. Brain Inj., 28(7):1003-1008.

[32]Yin, C., Guo, L.S., Liu, Y., et al., 2011. Repeated administration of propofol upregulated the expression of c-Fos and cleaved-caspase-3 proteins in the developing mouse brain. Indian J. Pharmacol., 43(6):648-651.

[33]Yu, D., Jiang, Y., Gao, J., et al., 2013. Repeated exposure to propofol potentiates neuroapoptosis and long-term behavioral deficits in neonatal rats. Neurosci. Lett., 534: 41-46.

[34]Yuen, V.M., 2010. Dexmedetomidine: perioperative applications in children. Paediatr. Anaesth., 20(3):256-264.

[35]Zhang, X., Wang, J., Qian, W., et al., 2014. Dexmedetomidine inhibits tumor necrosis factor-alpha and interleukin 6 in lipopolysaccharide-stimulated astrocytes by suppression of c-Jun N-terminal kinases. Inflammation, 37(3):942-949.