目的 观察针刺干预对脑缺血大鼠脑组织缺氧诱导因子1α(hypoxia-inducible factor-1α,HIF-1α)蛋白及mRNA表达的影响,探讨针刺对缺血性脑血管疾病的防治机制。方法 建立局灶性脑缺血大鼠模型,随机分为正常组、假手术组、模型组、针刺组(各8只大鼠),应用蛋白印迹及实时荧光定量检测针刺对局灶性脑缺血大鼠脑组织HIF-1α蛋白及mRNA表达的变化。结果 正常组和假手术组大鼠比较HIF-1α蛋白及mRNA表达无明显变化,模型组大鼠HIF-1α蛋白及mRNA表达上调,差异无统计学意义;针刺组大鼠HIF-1α蛋白及mRNA表达高于模型组(0.567±0.058 vs 0.315±0.118; 1.593±0.102 vs 1.193±0.259),差异有统计学意义(P<0.05)。结论 脑缺血后大鼠脑组织HIF-1α蛋白及mRNA表达增强,针刺可以上调其表达从而发挥脑保护作用。
Abstract
Objective To observe the effect of acupuncture on hypoxia inducible factor -1α and local cerebral blood flow in rats with focal cerebral ischemia.Methods Wistar rats were randomly divided into four groups:normal group, sham-operated group, model group and electroacupuncture(EA) group. Focal cerebral ischemia rat models were developed by middle cerebral artery occlusion(MCAO )with thread embolus. Electroacupuncture was applied to bilateral PC 6 and LI11 after MCAO. The expression of hypoxia inducible factor -1α was examined in MCAO rats by Western blot and real-time quantitative PCR (qPCR).Results Acupuncture could promote the recovery of neurological function in MCAO rats. Western blot and real-time qPCR showed that acupuncture promoted the hypoxia inducible factor -1α expression in the ischemic brain tissue with statistical significance(P<0.05).Conclusion Acupuncture promotes hypoxia inducible factor -1α expression in rats with focal cerebral ischemia. All the results suggest that the increased expression of hypoxia inducible factor -1α in the ischemic brain tissue plays an important role in brain protection.
关键词
局灶性脑缺血 /
针刺 /
缺氧诱导因子-1α
Key words
electroacupuncture /
focal cerebral ischemia /
hypoxia inducible factor -1α
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参考文献
[1] LU Yan,WANG Shi Jun,SONG Xiu Tao.Effects of electroacupuncture on glucose transporter-1 expression of hippocampal microvascular endothelial cells in rats with focal cerebral ischemia[J].Zhen Ci Yan Jiu,2010,35(2):118-123.
[2] 卢 岩,赵海军,王 媛,等.电针对局灶性脑缺血大鼠神经功能、脑血流及脑组织细胞色素P450表氧化酶基因表达的影响[J].针刺研究,2014, 39(5):345-350.
[3] Longa E Z,Weinstein P R,Carlson S,et al.Reversible middle cerebral artery occlusion without craniectomy in rats [J].Stroke,1989,20(1):84-91.
[4] 郭 义,方剑乔.实验针灸学实验指导[M].北京:中国中医药出版社,2012:46-49.
[5] 唐 曦,唐成林,徐放明,等.头针联合体针对亚急性期脑卒中患者肢体功能的影响[J].针刺研究,2012,37(6):488-492.
[6] Sharp F R,Bernaudin M.HIF1 and oxygen sensing in the brain [J].Nat Rev Neurosci, 2004,5(6):437-448.
[7] Shams I,Nevo E,Avivi A.Ontogenetic expression of erythropoietin and hypoxia-inducible factor-1 alpha genes in subterranean blind mole rats[J].FASEB J,2005,19(2):307-309.
[8] Ran R,Xu H,Lu A,et al.Hypoxia preconditioning in the brain[J].Dev Neurosci, 2005,27(2-4):87-92.
[9] Siddiq A,Aminova L R,Troy C M,et al.Selective inhibition of hypoxia-inducible factor (HIF) prolyl-hydroxylase 1 mediates neuroprotection against normoxic oxidative death via HIF-1and CREB-independent pathways[J].J Neurosci,2009,29(27):8828-8838.
[10] Siddiq A,Ayoubia I A,Chavez J C, et al.Hypoxia-inducible factor prolyl 4-hydroxylase inhibition. A target for neuroprotection in the central nervous system [J].J Biol Chem,2005,280(50):41732-41743.
[11] Zhou D,Matchett G A,Jadhav V,et al.The effect of 2-methoxyestradiol a HIF-1 alpha inhibitor, in global cerebral ischemia in rats[J].Neurol Res,2008,30(3):268-271.
[12] Rey S,Semenza G L.Hypoxia-inducible factor-1-dependent mechanisms of vascularization and vascular remodelling[J].Cardiovasc Res,2010,86(2):236-242.
[13] Lo E H,Dalkara T,Moskowitz M A.Mechanisms,challenges and opportunities in stroke[J].Nat Rev Neurosci,2003,4(5):399-415.
[14] Ke X J,ZhanG J J.Changes in HIF-1alpha,VEGF,NGF and BDNF levels in cerebrospinal fluid and their relationship with cognitive impairment in patients with cerebral infarction[J]. J Huazhong Univ Sci Technolog Med Sci,2013,33(3):433-437.
[15] Valle-Casuso J C, Gonzalez-Sanchez A,Medina J M,et al.HIF-1 and c-Src mediate increased glucose uptake induced by endothelin-1 and connexin43 in astrocytes[J].PLoS One,2012,7(2): e32448.
基金
国家自然科学基金青年项目(81102652),山东省自然科学基金(ZR2009CQ007)。
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