七氟烷通过影响神经元能量代谢和氧化应激水平促进神经元凋亡

doi:10.3969/j.issn.1009-976X.2022.01.005

摘要/Abstract

摘要： 目的研究吸入性麻醉药七氟烷对发育期神经元的凋亡作用,并探究七氟烷对原代神经元线粒体功能的影响。方法体外培养原代神经元,并随机分为对照组和实验组,实验组用4.1%七氟烷处理6 h,western blot检测Cleaved caspase-3凋亡蛋白的变化,流式细胞术检测神经元的凋亡率,DCFH-DA法检测细胞中ROS含量的变化,并检测ATP水平的变化。结果与对照组相比,七氟烷组的凋亡蛋白Cleaved caspase-3上调（P<0.01）,凋亡率增加（P<0.05）,ROS生成增加（P<0.05）同时ATP生成减少（P<0.05）。结论七氟烷可以诱导原代神经元的凋亡,其作用机制可能是通过线粒体能量代谢和氧化应激水平改变引起。

关键词: 七氟烷, 原代神经元, 凋亡, 能量代谢, 氧化应激

Abstract: Objective This paper investigates the neurotoxic effect of the anesthetic sevoflurane, and explores the influence of the energy metabolism and oxidative stress induced by sevoflurane. Methods Primary neurons were cultured in vitro and assigned into a control group and an experimental group. The experimental group was treated with 4.1% sevoflurane for 6 hours. Western blot was used to detect the change of Cleaved caspase-3 apoptotic protein, flow cytometry was used to detect the apoptotic rates of neurons, the DCFH-DA method was used to detect the change of ROS, and ATP is also detected by test kits. Results Compared with the control group, the cleaved caspase-3 apoptotic protein in experimental group increased （P<0.01）, the ROS also increased （P<0.05） but the ATP decreased （P<0.05）. Conclusion The sevoflurane-induced apoptosis may be caused by mitochondrial energy metabolism.

Key words: sevoflurane, primary neurons, apoptosis, energy metabolism, oxidative stress

中图分类号:

R614

张洋璠, 文金钡, 严颖哲, 黄晓燕, 谭梓聪, 杨浩杰, 纪风涛. 七氟烷通过影响神经元能量代谢和氧化应激水平促进神经元凋亡[J]. 岭南现代临床外科, 2022, 22(01): 30-33.

ZHANG Yang-fan, WEN Jin-bei, YAN Ying-zhe, HUANG Xiao-yan, TAN Zi-cong, YANG Hao-jie, JI Feng-tao. Sevoflurane induces neuronal apoptosis by affecting the energy metabolism and oxidative stress[J]. Lingnan Modern Clinics In Surgery, 2022, 22(01): 30-33.

参考文献

[1] Evered LA, Silbert BS.Postoperative Cognitive Dysfunction and Noncardiac Surgery[J]. Anesth Analg, 2018, 127(2): 496-505.
[2] Perez-Zoghbi JF, Zhu W, Grafe MR, et al.Dexmedetomidine-mediated neuroprotection against sevoflurane-induced neurotoxicity extends to several brain regions in neonatal rats[J]. Br J Anaesth, 2017, 119(3): 506-516.
[3] Xu L, Hu Y, Huang L, et al.The association between attention deficit hyperactivity disorder and general anaesthesia-a narrative review[J]. Anaesthesia, 2019, 74(1): 57-63.
[4] Lin MT, Beal MF.Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases[J]. Nature, 2006, 443(7113): 787-795.
[5] Wang Z, Meng S, Cao L, et al.Critical role of NLRP3-caspase-1 pathway in age-dependent isoflurane-induced microglial inflammatory response and cognitive impairment[J]. J Neuroinflammation, 2018, 15(1): 109.
[6] Ni C, Li Z, Qian M, et al.Isoflurane induced cognitive impairment in aged rats through hippocampal calcineurin/NFAT signaling[J]. Biochem Biophys Res Commun, 2015, 460(4): 889-895.
[7] Kaech S, Banker G.Culturing hippocampal neurons[J]. Nat Protoc, 2006, 1(5): 2406-2415.
[8] Zhu X, Yao Y, Guo M, et al.Sevoflurane increases intracellular calcium to induce mitochondrial injury and neuroapoptosis[J]. Toxicology Letters, 2021, 336: 11-20.
[9] Mccann ME, De Graaff JC, Dorris L, et al.Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS): an international, multicentre, randomised, controlled equivalence trial[J]. Lancet, 2019, 393(10172): 664-677.
[10] Li Y, Chen D, Wang H, et al.Intravenous versus Volatile Anesthetic Effects on Postoperative Cognition in Elderly Patients Undergoing Laparoscopic Abdominal Surgery[J]. Anesthesiology, 2021, 134(3): 381-394.
[11] Pellegrini L, Bennis Y, Velly L, et al.Erythropoietin protects newborn rat against sevoflurane-induced neurotoxicity[J]. Paediatr Anaesth, 2014, 24(7): 749-759.
[12] Gerkau NJ, Lerchundi R, Nelson JSE, et al.Relation between activity-induced intracellular sodium transients and ATP dynamics in mouse hippocampal neurons[J]. J Physiol, 2019, 597(23): 5687-5705.
[13] Yang XY, Li QJ, Zhang WC, et al.AMPK-SIRT1-PGC1alpha Signal Pathway Influences the Cognitive Function of Aged Rats in Sevoflurane-Induced Anesthesia[J]. J Mol Neurosci, 2020, 70(12): 2058-2067.
[14] Li J, Zhu X, Yang S, et al.Lidocaine Attenuates Cognitive Impairment After Isoflurane Anesthesia by Reducing Mitochondrial Damage[J]. Neurochem Res, 2019, 44(7): 1703-1714.
[15] Pougnet JT, Toulme E, Martinez A, et al.ATP P2X receptors downregulate AMPA receptor trafficking and postsynaptic efficacy in hippocampal neurons[J]. Neuron, 2014, 83(2): 417-430.
[16] Zhou H, Li S, Wang G.Euxanthone Ameliorates Sevoflurane-Induced Neurotoxicity in Neonatal Mice[J]. J Mol Neurosci, 2019, 68(2): 275-286.