Chronic intermittent hybobaric hypoxia protects against cerebral ischemia via modulation of mitoKATP

被引：13
作者：
Zhang, Shixiao [3 ]
Guo, Zan [1 ,2 ]
Yang, Shijie [4 ]
Ma, Huijuan [1 ,2 ]
Fu, Congrui [1 ]
Wang, Sheng [1 ,2 ]
Zhang, Yi [1 ,2 ]
Liu, Yixian [1 ,2 ]
Hu, Jie [3 ]
机构：
[1] Hebei Med Univ, Dept Physiol, 361 Zhongshan East Rd, Shijiazhuang 050017, Peoples R China
[2] Hebei Collaborat Innovat Ctr Cardiocerebrovasc Di, Shijiazhuang 050000, Peoples R China
[3] Hebei Med Univ, Dept Nursing, 361 Zhongshan East Rd, Shijiazhuang 050017, Peoples R China
[4] Hebei Med Univ, Dept Urol, Hosp 3, 139 Ziqiang Rd, Shijiazhuang 050051, Peoples R China
来源：
NEUROSCIENCE LETTERS | 2016年 / 635卷
关键词：
Chronic intermittent hypobaric hypoxia; Mitochondrial membrane ATPsensitive; potassium channel; Cytochrome c; 5-hydroxydecanoate; Mitochondrial membrane potential; SENSITIVE POTASSIUM CHANNEL; K-ATP CHANNEL; GERBIL HIPPOCAMPUS; BRAIN; NEUROPROTECTION; TOLERANCE; INJURY; RATS; MITOCHONDRIA; DEATH;
D O I：
10.1016/j.neulet.2016.10.025
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Objective: Providing adequate protection against cerebral ischemia remains an unrealized goal. The present study was aimed at testing whether chronic intermittent hypobaric hypoxia (CIHH) would have protective effects against cerebral ischemia and investigating the potential role of rriitochondrial membrane ATP-sensitive potassium channel (mitoK(ATP)) in this effect. Methods: Ischemia was induced in rats by occlusion of bilateral common carotid arteries for 8 min on day 2 after bilateral vertebral arteries were permanently electrocauterized and CIHH was simulated in a hypoxic chamber. Learning and memory impairments were analyzed using the Morris water maze. The delay neuronal death (DND) in the hippocampus CM was observed by thionine staining. The expression of the two subunits of mitoK(ATP), SUR1 and Kir 6.2, and the concentration of cytochrome c (Cyt c) were observed by Western blotting. The mitochondrial membrane potential (Delta ym) was determined by flow cytometry. Morphological changes of the mitochondria were investigated by electron microscopy. The antagonist of mitoK(ATP), 5-hydroxydecanoate (5-HD), was used to demonstrate the involvement of mitoK(ATP). Results: CIHH pretreatment ameliorated the learning and memory impairments produced by ischemia, concomitant with reduced DND in the hippocampus CM area. Expression levels of SUR1 and Kir6.2 both increased for at least one week after CIHH pretreatment. Levels of the two subunits were higher in the CIHH pretreatment combined with ischemia group than the ischemia only group at 2 d and 7 d after ischemia. Furthermore, the concentration of Cyt c was decreased in mitochondria and increased in the cytoplasm after ischemia which was prevented by CIHH. The decrease of Delta psi m and the destruction of mitochondrial ultrastructure were both rescued by CIHH pretreatment. The above protective effects of CIHH were blocked by 5-HD intraperitoneal injection 30 min before ischemia. Conclusion: CIHH pretreatment can reduce cerebral ischemic injury, which is mediated by upregulating the expression and activity of mitoK(ATP). (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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页码：8 / 16
页数：9
相关论文
共 27 条
  • [11] The role of glutamate transporter-1a in the induction of brain ischemic tolerance in rats
    Liu, Yi-Xian
    Zhang, Min
    Liu, Li-Zhe
    Cui, Xin
    Hu, Yu-Yan
    Li, Wen-Bin
    [J]. GLIA, 2012, 60 (01) : 112 - 124
  • [12] Mitochondrial plasticity in classical ischemic preconditioning -: moving beyond the mitochondrial KATP channel
    Minners, J
    McLeod, CJ
    Sack, MN
    [J]. CARDIOVASCULAR RESEARCH, 2003, 59 (01) : 1 - 6
  • [13] Chemical preconditioning prevents paradoxical increase in glutamate release during ischemia by activating ATP-dependent potassium channels in gerbil hippocampus
    Nakagawa, I
    Ogawa, Y
    Noriyama, Y
    Nakase, H
    Yamashita, M
    Sakaki, T
    [J]. EXPERIMENTAL NEUROLOGY, 2003, 183 (01) : 180 - 187
  • [14] ATP-dependent potassium channel mediates neuroprotection by chemical preconditioning with 3-nitropropionic acid in gerbil hippocampus
    Nakagawa, I
    Nakase, H
    Aketa, S
    Kamada, Y
    Yamashita, M
    Sakaki, T
    [J]. NEUROSCIENCE LETTERS, 2002, 320 (1-2) : 33 - 36
  • [15] Early-onset tolerance in rat global cerebral ischemia induced by a mitochondrial inhibitor
    Nakase, H
    Heimann, A
    Uranishi, R
    Riepe, MW
    Kempski, O
    [J]. NEUROSCIENCE LETTERS, 2000, 290 (02) : 105 - 108
  • [16] Presence and vascular pharmacology of KATP channel subtypes in rat central and peripheral tissues
    Ploug, Kenneth Beri
    Baun, Michael
    Hay-Schmidt, Anders
    Olesen, Jes
    Jansen-Olesen, Inger
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 2010, 637 (1-3) : 109 - 117
  • [17] Effects of intermittent hypoxic training on cycling performance in well-trained athletes
    Roels, Belle
    Bentley, David J.
    Coste, Olivier
    Mercier, Jacques
    Millet, Gregoire P.
    [J]. EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY, 2007, 101 (03) : 359 - 368
  • [18] Intermittent hypoxia: Cause of or therapy for systemic hypertension?
    Serebrovskaya, Tatiana V.
    Manukhina, Eugenia B.
    Smith, Michael L.
    Downey, H. Fred
    Mallet, Robert T.
    [J]. EXPERIMENTAL BIOLOGY AND MEDICINE, 2008, 233 (06) : 627 - 650
  • [19] Shu Y, 2016, J BIOL REG HOMEOS AG, V30, P41
  • [20] Kir6.2-containing ATP-sensitive potassium channels protect cortical neurons from ischemic/anoxic injury in vitro and in vivo
    Sun, H. -S.
    Feng, Z. -P.
    Barber, P. A.
    Buchan, A. M.
    French, R. J.
    [J]. NEUROSCIENCE, 2007, 144 (04) : 1509 - 1515
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