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脑低氧预适应及其机制

  • 简介: 原文 1 脑低氧预适应现象1986年Schurr等[3]就发现大鼠海马脑片低氧5 min后,其诱发电活动在随后长期低氧作用后仍能恢复,而对照组则不能。Rising等[4]事先给小鼠经90、120和150 s3次低氧(4.5%O2)预处理后,在致死量低氧作用下的存活时间由对...
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原文

1 脑低氧预适应现象
1986年Schurr等[3]就发现大鼠海马脑片低氧5 min后,其诱发电活动在随后长期低
氧作用后仍能恢复,而对照组则不能。Rising等[4]事先给小鼠经90、120和150 s
3次低氧(4.5%O2)预处理后,在致死量低氧作用下的存活时间由对照的(108±4)
s延长到(403±42) s。Vannucci等[5]在37℃下低氧(8%O2)预处理出生6 d的大鼠2
.5 h,24 h后结扎单侧颈总动脉并且低氧(8%O2)处理2.5 h,在出生第30天经神经
病理分析发现,低氧预适应组的14只大鼠中仅6只出现囊状梗死,而未预适应组的
13只大鼠都出现了梗死。
2 脑低氧预适应的可能机制
2.1 低氧诱导因子-1
低氧诱导因子-1(hypoxia-inducible factor-1,HIF-1)是一种随着细胞内氧浓度
变化而调节基因表达的转录激活因子,是由氧调节亚单位HIF-1α和结构亚单位HI
F-1β组成的异二聚体,具有DNA结合活性。HIF-1对低氧诱导基因,如促红细胞生
成素、糖酵解酶和血管内皮生长因子等的活化起关键作用。Bergeron等[6]通过对
新生大鼠脑低氧(8%O2)预处理3 h发现,低氧预处理可明显提高HIF-1α和HIF-1β
的表达水平。大鼠腹腔内注射HIF-1诱导剂氯化钴(CoCl2,60 mg/kg)和去铁铵(de
sferrioxamine,DFX,200 mg/kg)后1~3 h, HIF-1α和HIF-1β蛋白水平都升高。
大鼠经CoCl2和DFX预处理24 h后缺血缺氧可分别较对照组发挥75%和56%的脑保护
......


  目录

1 脑低氧预适应现象
2 脑低氧预适应的可能机制
3 脑低氧预适应的应用前景


  参考资料

参 考 文 献
1 Webster KA, Discher DJ, Bishopric NH. Cardioprotection in an in vitro
model of hypoxic preconditioning. J Mol Cell Cardiol, 1995, 27(1): 453
-458.
2 Heurteaux C, Lauritzen I, Widmann C, et al. Essential role of adenosi
ne, adenosine A1 receptors, and ATP-sensitive K+ channels in cerebral i
schemic preconditioning. Proc Natl Acad Sci USA, 1995, 92(10): 4666-467
0.
3 Schurr A, Reid KH, Tseng MT, et al. Adaptation of adult brain tissue
to anoxia and hypoxia in vitro. Brain Res, 1986, 374(2): 244-248.
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e
augmented by β-hydroxybutyrate in mice. Stroke, 1989, 20(9): 1219-122
5.
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oxic-ischemic brain damage in the immature rat: pathologic and metaboli
c correlates. J Neurochem, 1998, 71(3): 1215-1220.
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r-1 in hypoxia-induced ischemic tolerance in neonatal rat brain. Ann Ne
urol, 2000, 48(3): 285-296.
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cible factor 1 by oxygen glucose deprivation is attenuated by hypoxic p
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7-120.
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al ischemic tolerance in a neonatal rat model of hypoxic precondition
ing. J Cereb Blood Flow Metab, 1999, 19(3): 331-340.
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tured neurons against hypoxic stress via TNF-α and ceramide. Am J Phys
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14 Chen Y, Ginis I, Hallenbeck JM. The protective effect of ceramide in
immature rat brain hypoxia-ischemia involves up-regulation of bcl-2 an
d reduction of TUNEL-posit..


  简单介绍

摘要 预先反复短暂低氧预适应可使脑组织产生低氧适应,可使其在后续的长时间
缺氧中得到保护。脑低氧预适应是脑抗缺血或缺氧的一种内源性保护现象。目前对
脑低氧预适应的机制尚未最后阐明,文章对脑低氧预适应现象及其可能机制的研究
进展进行了综述。
低氧预适应(hypoxic preconditioning)是指1次或多次短暂、非致死性低氧刺激后
,机体获得的对更严重甚至致死性缺血或缺氧的耐受性。预适应是机体抗缺氧或缺
血的一种内源性保护现象,它不仅存在于多种动物的心脏,而且也存在于肝、肾和
脑等多种组织、器官和细胞中[1,2]。目前关于脑低氧预适应现象及其机制的报道
较少,深入研究脑低氧预适应机制并探讨其临床应用价值,对治疗脑血管病很有意
义。

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