Full Text:   <808>

Summary:  <250>

CLC number: R614.1

On-line Access: 2017-09-05

Received: 2016-10-19

Revision Accepted: 2016-12-18

Crosschecked: 2017-08-16

Cited: 0

Clicked: 1865

Citations:  Bibtex RefMan EndNote GB/T7714


Ke-zhong Li


-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2017 Vol.18 No.9 P.789-796


Neuroprotection of dexmedetomidine against propofol-induced neuroapoptosis partly mediated by PI3K/Akt pathway in hippocampal neurons of fetal rat

Author(s):  Ning Zhang, Quan-ping Su, Wei-xia Zhang, Nian-jun Shi, Hao Zhang, Ling-ping Wang, Zhong-kai Liu, Ke-zhong Li

Affiliation(s):  Department of Anesthesiology, the Second Hospital of Shandong University, Jinan 250033, China; more

Corresponding email(s):   likezhongsdu@163.com

Key Words:  Dexmedetomidine, Propofol, Neuroapoptosis, PI3K/Akt

Ning Zhang, Quan-ping Su, Wei-xia Zhang, Nian-jun Shi, Hao Zhang, Ling-ping Wang, Zhong-kai Liu, Ke-zhong Li. Neuroprotection of dexmedetomidine against propofol-induced neuroapoptosis partly mediated by PI3K/Akt pathway in hippocampal neurons of fetal rat[J]. Journal of Zhejiang University Science B, 2017, 18(9): 789-796.

@article{title="Neuroprotection of dexmedetomidine against propofol-induced neuroapoptosis partly mediated by PI3K/Akt pathway in hippocampal neurons of fetal rat",
author="Ning Zhang, Quan-ping Su, Wei-xia Zhang, Nian-jun Shi, Hao Zhang, Ling-ping Wang, Zhong-kai Liu, Ke-zhong Li",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Neuroprotection of dexmedetomidine against propofol-induced neuroapoptosis partly mediated by PI3K/Akt pathway in hippocampal neurons of fetal rat
%A Ning Zhang
%A Quan-ping Su
%A Wei-xia Zhang
%A Nian-jun Shi
%A Hao Zhang
%A Ling-ping Wang
%A Zhong-kai Liu
%A Ke-zhong Li
%J Journal of Zhejiang University SCIENCE B
%V 18
%N 9
%P 789-796
%@ 1673-1581
%D 2017
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1600476

T1 - Neuroprotection of dexmedetomidine against propofol-induced neuroapoptosis partly mediated by PI3K/Akt pathway in hippocampal neurons of fetal rat
A1 - Ning Zhang
A1 - Quan-ping Su
A1 - Wei-xia Zhang
A1 - Nian-jun Shi
A1 - Hao Zhang
A1 - Ling-ping Wang
A1 - Zhong-kai Liu
A1 - Ke-zhong Li
J0 - Journal of Zhejiang University Science B
VL - 18
IS - 9
SP - 789
EP - 796
%@ 1673-1581
Y1 - 2017
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1600476

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.


方法:首先分离胎鼠海马神经元并鉴定。使用MTT法检测异丙酚对神经元活性的影响。然后将神经元分为不同的组,分别用0.1、1、10和100 µmol/L右美托咪定预处理细胞,然后加入100 µmol/L的异丙酚继续培养,同时设异丙酚组和正常对照组。使用蛋白质印迹(Western blot)方法检测Akt、p-Akt、Bad、p-Bad和Bcl-xL的表达变化。在100 µmol/L右美托咪定预处理前加入LY294002,进一步研究PI3K/Akt途径是否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。
结论:实验结果显示,异丙酚明显降低了神经元的细胞活性及p-Akt和p-Bad的表达水平,增加了Bad的表达,从而Bcl-xL/Bad的比率升高。100 µmol/L右美托咪定预处理可以逆转这种效果。LY294002可以抑制右美托咪定的保护作用,说明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部分是由PI3K/Akt信号通路介导的。


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[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.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - Journal of Zhejiang University-SCIENCE