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浙江大学学报（医学版）
J Zhejiang Univ (Med Sci)  2019, Vol. 48 Issue (6): 668-673    DOI: 10.3785/j.issn.1008-9292.2019.12.12
    
Research progress on the effects of plateau hypoxia on blood-brain barrier structure and drug permeability
DING Yidan1,2(),LI Wenbin1,WANG Rong1,2,*(),ZHANG Jianchun3,*()
1. Key Laboratory of Plateau Environmental Damage Prevention, the 940 th Hospital of PLA Joint Logistics Support Force, Lanzhou 730050, China
2. School of Pharmacy, Lanzhou University, Lanzhou 730000, China
3. Department of Pharmacy, First Hospital of Chinese People's Liberation Army, Lanzhou 730000, China
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Abstract  

Drugs for the treatment of central nervous system diseases need to enter the brain tissue through the blood-brain barrier to function. In high altitude hypoxic environment, there are changes in tight junction proteins of blood-brain barrier tissue structure, transporters in astrocytes and endothelial cells and ATP in endothelial cells; at the same time the permeability of the blood-brain barrier is increased. These changes are an important reference for rational drug use in patients with central nervous system disease in the plateau region. This article reviews the research progress on the effects of plateau hypoxia on the structure of the blood-brain barrier and related drug permeability.

Key words： Central nervous system diseases      Blood-brain barrier      Altitude      Altitude sickness      Hypoxia, brain/physiopathology      Biological transport      Review     
Received: 22 August 2019      Published: 19 January 2020
CLC:  R594.3  
Corresponding Authors: WANG Rong,ZHANG Jianchun     E-mail: dingyd17@lzu.edu.cn;wangrong-69@163.com;zjc1508@126.com
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DING Yidan
LI Wenbin
WANG Rong
ZHANG Jianchun
Cite this article:

DING Yidan,LI Wenbin,WANG Rong,ZHANG Jianchun. Research progress on the effects of plateau hypoxia on blood-brain barrier structure and drug permeability. J Zhejiang Univ (Med Sci), 2019, 48(6): 668-673.

URL:

http://www.zjujournals.com/med/10.3785/j.issn.1008-9292.2019.12.12     OR     http://www.zjujournals.com/med/Y2019/V48/I6/668


高原低氧对血脑屏障结构及其药物通透性影响的研究进展

中枢神经系统疾病治疗药物需通过血脑屏障进入脑组织发挥作用。在高原低氧环境下，血脑屏障组织结构中的紧密连接蛋白、星型胶质细胞和内皮细胞上的转运蛋白、内皮细胞上的ATP发生变化，同时血脑屏障通透性增加。这些变化是高原地区中枢神经系统疾病患者的合理用药的重要参考。本文就高原低氧对血脑屏障结构及其药物通透性影响的研究进展作一综述。


关键词： 中枢神经系统疾病,  血脑屏障,  高海拔,  高原病,  缺氧, 脑/病理生理学,  生物转运,  综述 
[1]   LU H , WANG R , JIA Z P et al. Effects of high altitude exposure on physiology and pharmacokinetics[J]. Curr Drug Metab, 2016, 17 (6): 559- 565
doi: 10.2174/1389200216666151015113948
[2]   DEHNERT C , GRUNIG E , MERELES D et al. Identification of individuals susceptible to high-altitude pulmonary oedema at low altitude[J]. Eur Respir J, 2005, 25 (3): 545- 551
doi: 10.1183/09031936.05.00070404
[3]   QUAEGEBEUR A , CARMELIET P . Oxygen sensing:a common crossroad in cancer and neurodegeneration[J]. Curr Top Microbiol Immunol, 2010, 345 71- 103
[4]   BANKS W A . From blood-brain barrier to blood-brain interface:new opportunities for CNS drug delivery[J]. Nat Rev Drug Discov, 2016, 15 (4): 275- 292
doi: 10.1038/nrd.2015.21
[5]   ENGELHARDT S , PATKAR S , OGUNSHOLA O O . Cell-specific blood-brain barrier regulation in health and disease:a focus on hypoxia[J]. Br J Pharmacol, 2014, 171 (5): 1210- 1230
doi: 10.1111/bph.12489
[6]   LUKS A M , SWENSON E R , B?RTSCH P . Acute high-altitude sickness[J]. Eur Respir Rev, 2017, 26 (143): 1- 14
[7]   姜北芳, 刘威 . 缺氧状态下神经系统的改变和护理[J]. 中国实用医药, 2008, 3 (35): 183- 184
JIANG Beifang , LIU Wei . Changes and nursing of the nervous system in hypoxia[J]. China Practical Medicine, 2008, 3 (35): 183- 184
doi: 10.3969/j.issn.1673-7555.2008.35.159
[8]   KUMAR K V S H , SHIJITH K P , SINGH D . High altitude cerebral oedema[J]. Curr Med Res Pract, 2016, 6 (3): 126- 128
doi: 10.1016/j.cmrp.2016.03.008
[9]   WILLMANN G , GEKELER F , SCHOMMER K et al. Update on high altitude cerebral edema including recent work on the eye[J]. High Alt Med Biol, 2014, 15 (2): 112- 122
doi: 10.1089/ham.2013.1142
[10]   BAILEY D M , B?RTSCH P , KNAUTH M et al. Emerging concepts in acute mountain sickness and high-altitude cerebral edema:from the molecular to the morphological[J]. Cell Mol Life Sci, 2009, 66 (22): 3583- 3594
doi: 10.1007/s00018-009-0145-9
[11]   李虎, 王百忍, 巩固 . 高原脑水肿病理生理机制的研究进展[J]. 中华神经外科疾病研究杂志, 2016, 15 (4): 381- 384
LI Hu , WANG Bairen , GONG Gu . Research progress in pathophysiological mechanism of high altitude cerebral edema[J]. Chinese Journal of Neurosurgical Disease Research, 2016, 15 (4): 381- 384
[12]   LIN C , ZHAO X , SUN H . Analysis on the risk factors of intracranial infection secondary to traumatic brain injury[J]. Chin J Traumatol, 2015, 18 (2): 81- 83
doi: 10.1016/j.cjtee.2014.10.007
[13]   舒勤, 周明芳, 李巍 . 现代高原颅脑火器伤的救护重点[J]. 现代护理, 2007, 13 (1): 68- 69
SHU Qing , ZHOU Mingfang , LI Wei . Key points of rescue for modern high altitude craniocerebral firearm injury[J]. Modern Nursing, 2007, 13 (1): 68- 69
doi: 10.3760/cma.j.issn.1674-2907.2007.01.032
[14]   NAGARKATTI N , DESHPANDE L S , DELORENZO R J . Development of the calcium plateau following status epilepticus, role of calcium in epileptogenesis[J]. Expert Rev Neurother, 2009, 9 (6): 813- 824
doi: 10.1586/ern.09.21
[15]   VEZZANI A , FUJINAMI R S , WHITE H S et al. Infections, inflammation and epilepsy[J]. Acta Neuropathol, 2016, 131 (2): 211- 234
doi: 10.1007/s00401-015-1481-5
[16]   TAKESHITA Y , RANSOHOFF R M . Blood-brain barrier and neurological diseases[J]. Clin Exp Immunol, 2015, 6 351- 361
[17]   DING Y , WANG R , ZHANG J et al. Potential regulation mechanisms of P-gp in the blood-brain barrier in hypoxia[J]. Curr Pharm Design, 2019, 25 1- 9
doi: 10.2174/138161282501190514091805
[18]   FILOUS A R , SILVER J . Targeting astrocytes in CNS injury and disease:A translational research approach[J]. Prog Neurobiol, 2016, 144 173- 187
doi: 10.1016/j.pneurobio.2016.03.009
[19]   MCCAFFREY G , DAVIS T P . Physiology and pathophysiology of the blood-brain barrier:P-glycoprotein and occludin trafficking as therapeutic targets to optimize central nervous system drug delivery[J]. J Investig Med, 2012, 60 (8): 1131- 1140
doi: 10.2310/JIM.0b013e318276de79
[20]   ENGELHARDT S , AL-AHMAD A J , GASSMANN M et al. Hypoxia selectively disrupts brain microvascular endothelial tight junction complexes through a hypoxia-inducible factor-1(HIF-1) dependent mechanism[J]. J Cell Physiol, 2014, 229 (8): 1096- 1105
doi: 10.1002/jcp.24544
[21]   KAUR C , LING E A . Blood brain barrier in hypoxic-ischemic conditions[J]. Curr Neuro Res, 2008, 5 71- 81
doi: 10.2174/156720208783565645
[22]   EK C J , D'ANGELO B , BABURAMANI A A et al. Brain barrier properties and cerebral blood flow in neonatal mice exposed to cerebral hypoxia-ischemia[J]. J Cereb Blood Flow Metab, 2015, 35 (5): 818- 827
doi: 10.1038/jcbfm.2014.255
[23]   LOCHHEAD J J , RONALDSON P T , DAVIS T P . Hypoxic Stress and inflammatory pain disrupt blood-brain barrier tight junctions:implications for drug delivery to the central nervous system[J]. AAPS J, 2017, 19 (4): 910- 920
doi: 10.1208/s12248-017-0076-6
[24]   张明霞.高原缺氧对血脑屏障中药物转运蛋白的影响[D].兰州: 兰州大学, 2018.
ZHANG Mingxia. Effect of plateau hypoxia on drug transporter in blood-brain barrier[D]. Lanzhou: Lanzhou University, 2018. (in Chinese)
[25]   LOCHHEAD J J , MCCAFFREY G , QUIGLEY C E et al. Oxidative stress increases blood-brain barrier permeability and induces alterations in occludin during hypoxia-reoxygenation[J]. J Cereb Blood Flow Metab, 2010, 30 (9): 1625- 1636
doi: 10.1038/jcbfm.2010.29
[26]   KAUR C , SIVAKUMAR V , ZHANG Y et al. Hypoxia-induced astrocytic reaction and increased vascular permeability in the rat cerebellum[J]. Glia, 2006, 54 (8): 826- 839
doi: 10.1002/glia.20420
[27]   IORIO A L , MD R , FANTAPPIè O et al. Blood-brain barrier and breast cancer resistance protein:A limit to the therapy of CNS tumors and neurodegenerative diseases[J]. Anticancer Agents Med Chem, 2016, 16 (7): 810- 815
doi: 10.2174/1871520616666151120121928
[28]   HERMANN D M . Future perspectives for brain pharmacotherapies:Implications of drug transport processes at the blood-brain barrier[J]. Ther Adv Neurol Disord, 2008, 1 (3): 167- 179
[29]   张明霞, 王荣, 李文斌 et al. 高原缺氧对药物转运体影响的研究进展[J]. 中国药理学通报, 2018, 34 (3): 316- 321
ZHANG Mingxia , WANG Rong , LI Wenbin et al. Advances in the effects of plateau hypoxia on drug transporters[J]. Chinese Pharmacological Bulletin, 2018, 34 (3): 316- 321
doi: 10.3969/j.issn.1001-1978.2018.03.005
[30]   KINGWELL K . Drug delivery:New targets for drug delivery across the BBB[J]. Nat Rev Drug Discov, 2016, 15 (2): 84- 85
[31]   KOZIEL A , JARMUSZKIEWICZ W . Hypoxia and aerobic metabolism adaptations of human endothelial cells[J]. Pflugers Arch, 2017, 469 (5-6): 815- 827
doi: 10.1007/s00424-017-1935-9
[32]   LOSENKOVA K , ZUCCARINI M , HELENIUS M et al. Endothelial cells cope with hypoxia-induced depletion of ATP via activation of cellular purine turnover and phosphotransfer networks[J]. Biochim Biophys Acta Mol Basis Dis, 2018, 1864 (5 Pt A): 1804- 1815
[33]   BAILEY D M , TAUDORF S , BERG R M et al. Increased cerebral output of free radicals during hypoxia:implications for acute mountain sickness?[J]. Am J Physiol Regul Integr Comp Physiol, 2009, 297 (5): R1283- R1292
doi: 10.1152/ajpregu.00366.2009
[34]   郭平, 周其全, 罗涵 et al. 七叶皂苷钠对低氧暴露下大鼠血-脑脊液屏障通透性变化的影响及其抗渗漏机制研究[J]. 解放军医学杂志, 2012, 37 (2): 98- 103
GUO Ping , ZHOU Qiquan , LUO Han et al. Effects of sodium aescinate on blood-cerebrospinal fluid barrier permeability and its anti-leakage mechanism in rats exposed to hypoxia[J]. Medical Journal of Chinese People's Liberation Army, 2012, 37 (2): 98- 103
[35]   林驰, 宗希涛, 刘倩绫 et al. 亚高原高血压脑出血后继发癫痫的发生率及治疗的临床统计分析[J]. 立体定向和功能性神经外科杂志, 2016, 29 (6): 362- 364
LIN Chi , ZONG Xitao , LIU Qianling et al. Clinical analysis of the incidence and treatment of epilepsy after hypertensive intracerebral hemorrhage in subalpine[J]. Chinese Journal of Stereotactic and Functional Neurosurg, 2016, 29 (6): 362- 364
[36]   RATAN R R , SIDDIQ A , SMIRNOVA N et al. Harnessing hypoxic adaptation to prevent, treat, and repair stroke[J]. J Mol Med (Berl), 2007, 85 (12): 1331- 1338
doi: 10.1007/s00109-007-0283-1
[37]   AMIN M L . P-glycoprotein inhibition for optimal drug delivery[J]. Drug Target Insights, 2013, 7 27- 34
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