亚低温对脑缺血再灌注大鼠血管内皮生长因子和低氧诱导因子-1α表达的影响

doi:10.3969/j.issn.1006-9771.2017.06.010

《中国康复理论与实践》 ›› 2017, Vol. 23 ›› Issue (6): 667-671.doi: 10.3969/j.issn.1006-9771.2017.06.010

亚低温对脑缺血再灌注大鼠血管内皮生长因子和低氧诱导因子-1α表达的影响

程黎¹, 贾功伟²

1.重庆市急救医疗中心ICU,重庆市400010;
2.重庆医科大学附属第二医院康复医学科,重庆市 400010。

收稿日期:2017-02-21 修回日期:2017-03-31 出版日期:2017-06-25 发布日期:2017-06-27
通讯作者: 贾功伟,男,主治医师。E-mail: jiagongwei@163.com。
作者简介:程黎(1983-),女,汉族,湖北随州市人,硕士,医师,主要研究方向：神经康复。
基金资助:
重庆市卫生计生委2014年医学科研计划项目(No.20142077)

Effect of Mild Hypothermia on Expression of Vascular Endothelial Growth Factor and Hypoxia-inducible Factor-1α in Rats with Cerebral Ischemia-reperfusion

CHENG Li¹, JIA Gong-wei²

1. Department of ICU, Chongqing Emergency Medical Center, Chongqing 400010, China;
2. Department of Rehabilitation, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China

Received:2017-02-21 Revised:2017-03-31 Published:2017-06-25 Online:2017-06-27
Contact: Correspondence to JIA Gong-wei. E-mail: jiagongwei@163.com

摘要/Abstract

摘要： 目的探讨亚低温对脑缺血再灌注大鼠内皮生长因子(VEGF)和低氧诱导因子-1α (HIF-1α)表达的影响。方法 30只Sprague-Dawley大鼠随机分为假手术组、模型组和亚低温组,每组10只。后两组制备大脑中动脉闭塞(MCAO) 2 h再灌注动物模型,亚低温组进行亚低温处理24 h。Longa评分评估各组大鼠神经功能;湿/干重法测定脑含水量;TTC染色观察脑梗死体积;ELISA法检测脑组织VEGF、HIF-1α蛋白含量;qPCR法检测脑组织VEGF mRNA水平。结果与假手术组比,模型组神经行为学评分升高,脑含水量及脑梗死率增加,脑组织HIF-1α蛋白、VEGF蛋白及mRNA水平上调(P<0.05)。与模型组比,亚低温组神经神经行为学评分显著降低(χ²=26.657, P<0.001),脑含水量及脑梗死率降低,脑组织HIF-1α蛋白、VEGF蛋白及mRNA水平进一步上调(P<0.05)。结论亚低温可能通过HIF-1α介导VEGF上调,促进缺血组织区新生血管形成,从而发挥对缺血性脑卒中的保护作用。

关键词: 缺血再灌注, 亚低温, 血管内皮生长因子, 低氧诱导因子-1α, 大鼠

Abstract: Objective To observe the effect of mild hypothermia on expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) in brain tissues in rats with cerebral ischemia-reperfusion. Methods Thirty Sprague-Dawley rats were randomly divided into sham group, model group and mild hypothermia group with ten rats in each group. The latter two groups were established middle cerebral artery occlusion (MCAO) for two hours and reperfusion model. The mild hypothermia group received mild hypothermia treatment for 24 hours. The neurologic function was evaluated with Longa's score. The brain water content was measured by wet/dry method. The infarction area ratio was assessed by TTC staining. The protein levels of VEGF and HIF-1α were determined by ELISA, while the mRNA level of VEGF was assessed by qPCR. Results Compared with the sham group, the score of neurologic score, the brain water content ratio and the infarction area ratio, the expression of VEGF protein and HIF-1α protein, and the mRNA level of VEGF increased in the model group (P<0.05). Compared with the model group, the score of neurologic score significantly decreased (χ²=26.657, P<0.001), the brain water content ratio and the infarction area ratio decreased (P<0.05), and the expression of VEGF protein and HIF-1α protein, and the mRNA level of VEGF further increased (P<0.05) in the mild hypothermia group. Conclusion Mild hypothermia may protect against ischemic-induced neurologic injury by up-regulating the expression of VEGF and HIF-1α, and promote the angiogenesis in the rats with cerebral ischemia-reperfusion.

Key words: ischemia-reperfusion, mild hypothermia, vascular endothelial growth factor, hypoxia-inducible factor-1α, rats

中图分类号:

R743.3

程黎, 贾功伟. 亚低温对脑缺血再灌注大鼠血管内皮生长因子和低氧诱导因子-1α表达的影响[J]. 《中国康复理论与实践》, 2017, 23(6): 667-671.

CHENG Li, JIA Gong-wei. Effect of Mild Hypothermia on Expression of Vascular Endothelial Growth Factor and Hypoxia-inducible Factor-1α in Rats with Cerebral Ischemia-reperfusion[J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2017, 23(6): 667-671.

参考文献

[1] Doyle KP, Simon RP, Stenzel-Poore MP. Mechanisms of ischemic brain damage [J]. Neuropharmacology, 2008, 55(3): 310-318.
[2] Moskowitz MA, Lo EH, Iadecola C. The science of stroke: mechanisms in search of treatments [J]. Neuron, 2010, 67(2): 181-198.
[3] Yang G, Wang Y, Zeng Y, et al. Rapid health transition in China, 1990-2010: findings from the Global Burden of Disease Study 2010 [J]. Lancet, 2013, 381(9882): 1987-2015.
[4] Navarro-Sobrino M, Rosell A, Hernandez-Guillamon M, et al. A large screening of angiogenesis biomarkers and their association with neurological outcome after ischemic stroke [J]. Atherosclerosis, 2011, 216(1): 205-211.
[5] Ohab JJ, Fleming S, Blesch A, et al. A neurovascular niche for neurogenesis after stroke [J]. J Neurosci, 2006, 26(50): 13007-13016.
[6] Marti HH, Risau W. Angiogenesis in ischemic disease [J]. Thromb Haemost, 1999, 82(Suppl 1): 44-52.
[7] Greenberg DA, Jin K. From angiogenesis to neuropathology [J]. Nature, 2005, 438(7070): 954-959.
[8] Griffiths L, Dachs GU, Bicknell R, et al. The influence of oxygen tension and pH on the expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase in human breast tumor cells grown in vitro and in vivo [J]. Cancer Res, 1997, 57(4): 570-572.
[9] Karakashev SV, Reginato MJ. Hypoxia/HIF1alpha induces lapatinib resistance in ERBB2-positive breast cancer cells via regulation of DUSP2 [J]. Oncotarget, 2015, 6(4): 1967-1980.
[10] Pereira ER, Frudd K, Awad W, et al. Endoplasmic reticulum (ER) stress and hypoxia response pathways interact to potentiate hypoxia-inducible factor 1 (HIF-1) transcriptional activity on targets like vascular endothelial growth factor (VEGF) [J]. J Biol Chem, 2014, 289(6): 3352-3364.
[11] Van Der Worp HB, Macleod MR, Bath PM, et al. EuroHYP-1: European multicenter, randomized, phase III clinical trial of therapeutic hypothermia plus best medical treatment vs. best medical treatment alone for acute ischemic stroke [J]. Int J Stroke, 2014, 9(5): 642-645.
[12] Wu TC, Grotta JC. Hypothermia for acute ischaemic stroke [J]. Lancet Neurol, 2013, 12(3): 275-284.
[13] 李飞,李树清. 亚低温后适应对树鼩局部脑缺血海马CA1区神经元的保护机制[J]. 中国病理生理杂志, 2009, 25(2): 236-240.
[14] Longa EZ, Weinstein PR, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats [J]. Stroke, 1989, 20(1): 84-91.
[15] Liu S, Cao Y, Qu M, et al. Curcumin protects against stroke and increases levels of Notch intracellular domain [J]. Neurol Res, 2016, 38(6): 553-559.
[16] Heiss WD. The ischemic penumbra: how does tissue injury evolve? [J]. Ann N Y Acad Sci, 2012, 1268: 26-34.
[17] Sims NR, Muyderman H. Mitochondria, oxidative metabolism and cell death in stroke [J]. Biochim Biophys Acta, 2010, 1802(1): 80-91.
[18] Emerich DF, Silva E, Ali O, et al. Injectable VEGF hydrogels produce near complete neurological and anatomical protection following cerebral ischemia in rats [J]. Cell Transplant, 2010, 19(9): 1063-1071.
[19] Matsuo R, Ago T, Kamouchi M, et al. Clinical significance of plasma VEGF value in ischemic stroke – research for biomarkers in ischemic stroke (REBIOS) study [J]. BMC Neurol, 2013, 13: 32.
[20] Sun Y, Jin K, Xie L, et al. VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia [J]. J Clin Invest, 2003, 111(12): 1843-1851.
[21] Wang Y, Galvan V, Gorostiza O, et al. Vascular endothelial growth factor improves recovery of sensorimotor and cognitive deficits after focal cerebral ischemia in the rat [J]. Brain Res, 2006, 1115(1): 186-193.
[22] 官俏兵,张晓玲,王琰萍,等. 血清血管生长因子浓度变化与急性脑梗死后神经功能康复的关系[J]. 实用医学杂志, 2013, 29(5): 726-728.
[23] Nakamura H, Tasaki L, Kanoh D, et al. Diaryl-substituted ortho-carboranes as a new class of hypoxia inducible factor-1alpha inhibitors [J]. Dalton Trans, 2014, 43(13): 4941-4944.
[24] Liu Q, Geng H, Xue C, et al. Functional regulation of hypoxia inducible factor-1alpha by SET9 lysine methyltransferase [J].Biochim Biophys Acta, 2015, 1853(5): 881-891.
[25] Schwartz DL, Bankson J, Bidaut L, et al. HIF-1-dependent stromal adaptation to ischemia mediates in vivo tumor radiation resistance [J]. Mol Cancer Res, 2011, 9(3): 259-270.

亚低温对脑缺血再灌注大鼠血管内皮生长因子和低氧诱导因子-1α表达的影响

Effect of Mild Hypothermia on Expression of Vascular Endothelial Growth Factor and Hypoxia-inducible Factor-1α in Rats with Cerebral Ischemia-reperfusion

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

Metrics

本文评价

推荐阅读 0

[1]	李芳, 霍速, 杜巨豹, 刘秀贞, 李小爽, 宋为群. 经颅直流电刺激联合任务导向性康复训练对脊髓损伤大鼠前肢运动障碍的效果[J]. 《中国康复理论与实践》, 2023, 29(7): 777-781.
[2]	康晓宇, 刘丽旭, 王文竹, 王云雷. 普拉克索联合左旋多巴对全脑缺血再灌注损伤大鼠认知能力及线粒体功能的影响[J]. 《中国康复理论与实践》, 2023, 29(5): 533-540.
[3]	罗兰, 李璐, 金沐. 氙气后处理对脊髓缺血再灌注损伤的效果：Akt信号通路和自噬机制[J]. 《中国康复理论与实践》, 2023, 29(2): 174-181.
[4]	黄志霖, 徐发邵, 施静, 黄淦, 刘梅芳, 张霞辉. 线栓法建立卒中后吞咽障碍的大鼠模型[J]. 《中国康复理论与实践》, 2023, 29(10): 1147-1153.
[5]	秦彦强, 董浩, 孙迎春, 程先宽, 姚海江. 不同针刺方案对卒中后抑郁大鼠神经递质及相关炎性因子的影响[J]. 《中国康复理论与实践》, 2023, 29(1): 30-37.
[6]	缪培,张通,米海霞,张伟东. 不同线栓法复制局灶性脑缺血模型大鼠恢复期学习记忆能力的差异及其机制[J]. 《中国康复理论与实践》, 2022, 28(7): 789-796.
[7]	周小珏,冯婧,庞日朝,刘捷,张安仁. 隔日限食减轻脊髓损伤大鼠炎症反应的芳香烃受体/细胞因子信号传导抑制因子2/核转录因子-κB信号通路机制[J]. 《中国康复理论与实践》, 2022, 28(5): 544-551.
[8]	宋绍霏,侯园园,王云雷,张通. 异常光周期所致昼夜节律紊乱对大鼠腓肠肌时钟基因和葡萄糖摄取相关基因表达节律的影响[J]. 《中国康复理论与实践》, 2022, 28(5): 552-558.
[9]	黄菲菲,王万松,董晓阳,冯珍. 高压氧修复缺血再灌注损伤大鼠血脑屏障的自噬机制[J]. 《中国康复理论与实践》, 2022, 28(4): 415-420.
[10]	李童,方志鹏,邵玉萍,王平. 有氧运动对睡眠剥夺大鼠学习记忆及海马神经元突触可塑性的效果[J]. 《中国康复理论与实践》, 2022, 28(11): 1270-1277.
[11]	王静怡,尹杰,刘建成,庞日朝,王文春. 蜘蛛香环烯醚萜类成分对急性脊髓损伤大鼠神经细胞焦亡的影响[J]. 《中国康复理论与实践》, 2021, 27(6): 653-660.
[12]	周文美,陶陶,吴霜,王廷龙,杨正奕,张莹. 丰富环境对脑缺血再灌注损伤大鼠神经功能和缺血半暗带区葡萄糖代谢的影响[J]. 《中国康复理论与实践》, 2021, 27(5): 522-529.
[13]	王琼芬,王风波,王科,钟永强,王娇娇. 电针风池对急性脑梗死大鼠脑星形胶质细胞和神经元的保护效果[J]. 《中国康复理论与实践》, 2021, 27(3): 302-309.
[14]	李向哲,丁洁,王庆华,董传明,王彤,吴勤峰. 减重平板训练对脊髓损伤大鼠神经病理性疼痛及脊髓后角谷氨酸脱羧酶-65/67表达的影响[J]. 《中国康复理论与实践》, 2021, 27(2): 131-136.
[15]	艾坤,许明,刘琼,邓石峰,刘继生,祁芳,易细芹,瞿启睿,张泓. 电针对骶上脊髓损伤后逼尿肌亢进大鼠逼尿肌中环腺苷酸和蛋白激酶A含量及肌球蛋白轻链激酶磷酸化的影响[J]. 《中国康复理论与实践》, 2021, 27(2): 137-144.