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脑缺血预处理对神经元神经钙调磷酸酶及磷酸化蛋白激酶B表达的影响 被引量:2

Effect of cerebral ischemic preconditioning on the expression of calcineurin and phosphorylated protein kinase B in neurons
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摘要 目的研究脑缺血预处理(CIPC)对神经元神经钙调磷酸酶(CaN)及磷酸化蛋白激酶B(p-AKT)表达的影响。方法雄性SD大鼠108只,随机分为假手术组、脑缺血组、CIPC组、尼莫地平组、环孢素A组及LY294002组,每组18只。评价各组大鼠神经功能缺损;计算脑梗死体积;检测CaN及p-AKT蛋白表达。结果与脑缺血组比较,CIPC组、尼莫地平组和环孢素A组神经功能缺损评分和脑梗死体积明显降低(P<0.05,P<0.01)。与假手术组比较,其他5组CaN蛋白表达明显升高(P<0.01);与脑缺血组比较,CIPC组、LY294002组CaN蛋白表达降低(P<0.05);与CIPC组比较,尼莫地平组和环孢素A组CaN蛋白表达明显降低(P<0.05,P<0.01)。除LY294002组外,余各组p-AKT蛋白表达与CaN蛋白相反。结论 CIPC降低神经元CaN表达,提高p AKT表达,提供神经保护。尼莫地平和环孢素A增强了神经保护。LY294002抵消了CIPC的保护作用。 Objective To study the effect of cerebral ischemic preconditioning(CIPC) on the expression of calcineurin(CaN) and phosphorylated protein kinase B(p-AKT) in hippocampus neu- rons. Methods 108 adult healthy male SD rats were randomly divided into sham operation group, brain ischemia group, CIPC groups, nimodipine group, cyclosporine A group, and LY294002 group. There were 18 rats in each group. The neurological deficit scores were evaluated,the volume of the cerebral infarct was calculated. The expression of CaN and p-AKT at protein level was examined by Western blot. Results The neurological deficit scores and the volume of the cerebral infarct were highest in the ischemia and LY294002 groups,these items in the CIPC group,the ni modipine group and the cyclosporine A group were lower than those in the ischemia group (P 〈 0.05,P 〈 0.01). The expression of CaN was highest in the ischemia group,it was lower in the CIPC and LY294002 groups than in ischemia group (P 〈 0.05), and was lowest in the nimodipine and cyclosporine A groups (P 〈 0.05 ,P 〈 0.01). The expression of p-AKT was lowest in the ischemia and LY294002 groups,and was higher in the CIPC group than in the ischemia group (P 〈 0.05) ;it was highest in the nimodipine and cyclosporine A groups (P 〈 0.05, P 〈 0.01). Conclusions Continuous ischemia increases the expression of CaN, and reduces the expression of p-AKT. CIPC reduces the expression of CaN, and raises the expression of p-AKT, thereby increasing cerebral ischemic tolerance. Nimodipine and cyclosporine A can reduce the expression of CaN,and increase the expression of p-AKT. LY294002 counteracts the neuroprotection of CIPC.
出处 《中华老年心脑血管病杂志》 CAS 北大核心 2011年第6期557-560,共4页 Chinese Journal of Geriatric Heart,Brain and Vessel Diseases
关键词 脑缺血 缺血预处理 神经元 蛋白激酶类 磷酸化酶激酶 尼莫地平 脑梗死 brain ischemia ischemic preconditioning neurons protein kinases phosphorylase ki nase nimodipine brain infarction
作者简介 通讯作者:尹琳.Email:andreas2005@vip.sina.com
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参考文献11

  • 1Abhisek M,Diego MS,Dennisse GR,et al.Calcineurin inhibition at the clinical phase of prion disease reduces neurodegen-eration,improves behavioral alterations and increases animal survival.PLoS Pathog,2010,6:e1001-138.
  • 2Zhang Y,Park TS,Gidday JM.Hypoxic preconditioning protects human brain endothelium from ischemic apoptosis by Akt-dependent survivin activation.Am J Physiol Heart Circ Physiol,2007,292:2573-2581.
  • 3姜长斌,丁聪,尹琳.脑缺血预处理大鼠脑IL-6和Ngb的表达及尤瑞克林对其表达的干预[J].中国神经免疫学和神经病学杂志,2009,16(1):42-46. 被引量:8
  • 4Li Q,Li Z,Xu XY,et al.Neuroprotective properties of picro-side II in a rat model of focal cerebral ischemia.Int J Mol Sci,2010,11:4580-4590.
  • 5姜永梅,张慧,尹琳.脑缺血预处理对海马神经元内游离钙离子的影响[J].中风与神经疾病杂志,2010,27(10):928-930. 被引量:1
  • 6Bickler PE,Fahlman CS,Gray J,et al.Inositol 1,4,5-triphos-phate receptors and NAD(P)H mediate Ca2 + signaling re quired for hypoxic preconditioning of hippocampal neurons.Neuroscience,2009,160:51 -60.
  • 7Kim MS,Usachev YM.Mitochondrial Ca2+cycling facilitates activation of the transcription factor NFAT in sensory neurons.J Neurosci,2009,29:12101-12114.
  • 8Shioda N,Han F,Moriguchi S,et al.Constitutively active calcineurin mediates delayed neuronal death through Fas-ligand expression via activation of NFAT and FKHR transcriptional activities in mouse brain ischemia.J Neurochem,2007,102:1506-1517.
  • 9Wen JY,Chen ZW.Protective effect of pharmacological preconditioning of total flavones of abelmoschlmanihot on cerebral ischemic reperfusion injury in rats.Am J Chin Med,2007,35:653-661.
  • 10Yin W,Signore AP,Iwai M,et al.Preconditioning suppresses inflammation in neonatal hypoxic ischemia via Akt activation.Stroke,2007,38:1017-1024.

二级参考文献26

  • 1黄勇华,张微微,郝小淑,王伟,王军,谢荣堂.钙离子与鼠脑出血继发性损伤的关系及尼莫地平的保护作用[J].中华老年心脑血管病杂志,2000,2(3):200-202. 被引量:13
  • 2尹琳,李芳,金萍,闵连秋.脑缺血预处理对再次脑缺血大鼠神经功能、脑含水量及脑组织中Bcl-xl和P53蛋白表达的影响[J].中国临床康复,2005,9(1):110-112. 被引量:1
  • 3吕少萍,管勇.尼莫通对脑缺血再灌注细胞凋亡相关基因表达影响[J].青岛大学医学院学报,2005,41(2):167-168. 被引量:2
  • 4Chen J, Simon R. Ischemic tolerance in the brain [J]. Neurology,1997, 48(2): 306-311.
  • 5Kitagawa K, Matsumoto M, Tagaya M, et al. "Is chemic tolerance" phenomenon found in the brain [J].Brain Res, 1990, 528(1): 21-24.
  • 6Fredrik LM, Lundberg L, Marceau F, etal. Classification of the kinin receptor family: from molecular mechanisms to pathophysiological consequences [J]. Pharmacol Rev, 2005, 57(1): 27-77.
  • 7Emanueli C, Madeddu P. Angiogenesis therapy with human tissue kallikrein for the treatment of ischemic diseases[J]. Arch Mal Coeur, 2004, 97: 679-687.
  • 8Koizumi J, Yoshida Y, Nakazawa T, et al. Experimental studies of ischemic brain edema: a new experimental model of cerebral embolism in rats in which recirculation can be introduced in the ischemic area[J]. Jpn J Stroke, 1986, 8: 1-8.
  • 9Bederson JB, Pitts LH, Tsuji M, et al. Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination[J]. Stroke, 1986, 17(3): 472-476.
  • 10Moncayo J, de Freitas GR, Bogousslaky J, et al. Do transient ischemic attacks have a neural protective effect? [J]. Neurology, 2000, 54(11): 2089-2094.

共引文献7

同被引文献36

  • 1陈迁,熊志奇.NMDA受体NR2A亚单位特异性地参与脑损伤导致的颞叶癫痫病[J].中国基础科学,2007(2):22-27. 被引量:36
  • 2陈小睿,唐光曦,孟宪丽,黄雷雷,李佳川.基于PI3K/Akt信号转导通路的通脉醒脑滴丸治疗脑缺血的机制研究[J].时珍国医国药,2010,21(12):3143-3145. 被引量:7
  • 3Di Lorenzo A, Fernandez - Hernando C, Cirino G, et al. AKTI is critical for acute inflammation and hista- mine- mediated vascular leakage [ J]. Proc Natl Acad Sci USA, 2009, 106 (34): 14552-14557.
  • 4Lee D, Do IG, Choi K, et al. The expression of phospho -AKT1 and phos - phor -MTOR is associat- ed with a favorable prognosis independent of PTEN ex- pression in intrah- epatic eholangiocarcinomas [ J]. Modern Pathology, 2012, 25: 131-139.
  • 5Yuan TL, Cantley LC. PI3K pathway aheration in cancer: variation on a theme [J]. Oncogen, 2008, 27 (41): 5497-5510.
  • 6Pilling C, Landgraf KE, Falke JJ. The GRP1 PH do- main, like the AKT1 PH Domain, possesses a sentry glutamate residue essential for specific targeting to plas- mamembrane PI (3, 4, 5) P3 [J]. Biochemistry, 2011, 50 (45): 9845-9856.
  • 7Wu D, Pei D, Wang Q, et al. Down- regulation of PTEN by sodium orthovanadate inhibits Askl activation via PI3K/AKTI during cerebral ischemia in rat hippo- campus [J]. Neurosci Lett, 2006, 404:98-102.
  • 8Kohayashi I, Semha S, MatsudaY, et al. Significance of AKT phosphorylation on tumor growth and vascular endothelial growth factor expression in human gastric carcinoma [J]. Pathobiology, 2006, 75 ( 1 ) : 8 - 17.
  • 9Yoon K, Jung E J, Lee SY. TRAF - 6 mediated regu- lation of the PI3kinase (PI3K) - AKT - GSK 3beta cascade is required for TNF - induced cell survival [J]. Biochem Biophys Res Commun, 2008, 371 (1): 118-121.
  • 10Mullonkal C J, Toledo -Pereyra LH. AKT in ischemia and reperfusion[ J ]. Invest Surg, 2007, 20 ( 3 ) : 195 - 203.

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