常压高浓度氧下调电压依赖性阴离子通道蛋白对脑缺血-再灌注损伤大鼠的保护作用

doi:10.3969/j.issn.1006-7795.2017.01.009

首都医科大学学报 ›› 2017, Vol. 38 ›› Issue (1): 42-46.doi: 10.3969/j.issn.1006-7795.2017.01.009

• 脑血管病、认知障碍的基础及临床研究 • 上一篇下一篇

常压高浓度氧下调电压依赖性阴离子通道蛋白对脑缺血-再灌注损伤大鼠的保护作用

师文娟, 戚智锋, 刘克建

首都医科大学宣武医院北京市老年病医疗研究中心脑血管病研究室, 北京 100053

收稿日期:2016-11-28 出版日期:2017-01-21 发布日期:2017-01-20
通讯作者: 刘克建 E-mail:kliu@salud.unm.edu
基金资助:
国家自然科学基金项目（81620108011，81571175），北京市科技新星项目（Z141107001814045）资助。

Normobaric hyperoxia protect cerebral ischemia/reperfusion injured rats by downregulating voltage-dependent anion channel protein

Shi Wenjuan, Qi Zhifeng, Liu Kejian

Xuanwu Hospital, Capital Medical University, Beijing Geriatric Medical Research Center, Cerebrovascular Diseases Research Institute, Beijing 100053, China

Received:2016-11-28 Online:2017-01-21 Published:2017-01-20
Supported by:
This study was supported by National Natural Science Foundation of China (81620108011,81571175), Beijing Nova Program (Z141107001814045).

摘要/Abstract

摘要： 目的观察常压高浓度氧治疗（normobaric hyperoxia，NBO）对脑缺血-再灌注大鼠电压依赖性阴离子通道蛋白（voltage-dependent anion channel，VDAC）以及凋亡蛋白细胞色素C（cytochrome C，CytC）和活化型半胱天冬酶-3（cleaved caspase-3）的影响，初步探讨其作用机制。方法将15只健康成年雄性SD大鼠（280~320 g）采用数字表法分为3组：假手术组（Sham）、正常氧浓度组（Normoxia）和NBO组，采用线栓法制备大鼠大脑中动脉阻塞模型，模型大鼠缺血1.5 h，再灌注24 h。Sham组和Normoxia组大鼠术后呼吸普通空气，NBO组大鼠术后至再灌注前呼吸100%常压氧气。采用Western blotting方法，检测脑缺血半影区VDAC、CytC和cleaved caspase-3蛋白的表达变化。结果 1）与Sham组相比，Normoxia组缺血侧半影区VDAC显著升高（P<0.05）；与Normoxia组相比，NBO组缺血侧半影区VDAC显著降低（P<0.05）；2）与Normoxia组相比，NBO组缺血侧半影区凋亡蛋白CytC和cleaved caspase-3显著减少（P<0.05）。结论 NBO治疗可能通过调节缺血侧半影区电压依赖性阴离子通道蛋白VDAC的表达来抑制脑缺血诱发的细胞凋亡，从而实现脑神经保护作用。

关键词: 脑缺血-再灌注, 常压高浓度氧, 电压依赖性阴离子通道蛋白, 凋亡

Abstract: Objective To observe the effect of normobaric hyperoxia (NBO) on expression of voltage-dependent anion channel (VDAC), cytochrome C (CytC) and cleaved caspase-3 induced by cerebral ischemia-reperfusion injury in rats, and preliminarily explore the mechanism of NBO treatment on prevention of apoptosis. Methods Fifteen healthy adult male Sprague-Dawley (SD) rats (280-320 g) were divided randomly into three groups:Sham group (n=3), Normoxia group (n=6) and NBO group (n=6). A model operation of MCAO was performed using intraluminal suture method. The rats underwent MCAO for 1.5 h plus 24 h reperfusion. After model operation the rats of sham group and normoxia group breathed normal air, and instead NBO group rats breathed 100% oxygen until reperfusion. Western blotting was used to test the expression of VDAC, CytC and cleaved caspase-3 protein in ischemic penumbra region. Results Western blotting results showed that compared with the sham group, the VDAC protein expression of ischemic penumbra was increased (P<0.05) in the normoxia group, and compared with the normoxia group, the expression of VDAC protein in ischemic penumbra region was statistically significantly reduced (P<0.05) in NBO group. Compared with the normoxia group, the expressions of CytC protein and cleaved caspase-3 protein in ischemic penumbra region were statistically significantly decreased (P<0.05) in NBO group. Conclusion NBO treatment may inhibit cerebral ischemia-induced apoptosis by downregulating the excessive expression of voltage-dependent anion channel protein in ischemic penumbra region, thus to play a protective role in the ischemia/reperfusion injured brain.

Key words: cerebral ischemia-reperfusion, normobaric hyperoxia(NBO), voltage-dependent anion channel(VDAC), apoptosis

中图分类号:

R743.3

师文娟, 戚智锋, 刘克建. 常压高浓度氧下调电压依赖性阴离子通道蛋白对脑缺血-再灌注损伤大鼠的保护作用[J]. 首都医科大学学报, 2017, 38(1): 42-46.

Shi Wenjuan, Qi Zhifeng, Liu Kejian. Normobaric hyperoxia protect cerebral ischemia/reperfusion injured rats by downregulating voltage-dependent anion channel protein[J]. Journal of Capital Medical University, 2017, 38(1): 42-46.

参考文献

[1] Shoshan-Barmatz V, Ben-Hail D. VDAC, a multi-functional mitochondrial protein as a pharmacological target[J]. Mitochondrion, 2012, 12(1):24-34.
[2] Mertins B, Psakis G, Essen L O. Voltage-dependent anion channels:the wizard of the mitochondrial outer membrane[J]. Biol Chem, 2014, 395(12):1435-1442.
[3] Liao Z, Liu D, Tang L, et al. Long-term oral resveratrol intake provides nutritional preconditioning against myocardial ischemia/reperfusion injury:involvement of VDAC1 downregulation[J]. Mol Nutr Food Res, 2015, 59(3):454-464.
[4] Liu S, Liu W, Ding W, et al. Electron paramagnetic resonance-guided normobaric hyperoxia treatment protects the brain by maintaining penumbral oxygenation in a rat model of transient focal cerebral ischemia[J]. J Cereb Blood Flow Metab, 2006, 26(10):1274-1284.
[5] Wu O, Benner T, Roccatagliata L, et al. Evaluating effects of normobaric oxygen therapy in acute stroke with MRI based predictive models[J]. Med Gas Res, 2012, 2(1):5.
[6] Dong W, Qi Z, Liang J, et al. Reduction of zinc accumulation in mitochondria contributes to decreased cerebral ischemic injury by normobaric hyperoxia treatment in an experimental stroke model[J]. Exp Neurol, 2015, 272:181-189.
[7] Tajiri N, Dailey T, Metcalf C, et al. In vivo animal stroke models:a rationale for rodent and non-human primate models[J]. Transl Stroke Res, 2013, 4(3):308-321.
[8] 刘晓婷,王延让,张明. 线粒体介导细胞凋亡的研究进展[J]. 环境与健康杂志, 2013, 30(2):182-184.
[9] Norberq E, Orrenius S, Zhivotovsky B. Mitochondrial regulation of cell death:processing of apoptosis-inducing factor (AIF)[J]. Biochem Biophys Res Commun, 2010, 396(1):95-100.
[10] 房亚兰, 罗玉敏,赵咏梅. 大黄对缺血性脑血管病的保护作用及机制研究[J]. 首都医科大学学报, 2015,36(5):718-722.
[11] 岳志伟, 刘强,陈乃耀. 创伤性脑损伤和线粒体功能障碍[J]. 中国煤炭工业医学杂志,2016,19(4):645-650.
[12] 冯政哲, 张海峰,于瀛,等.线粒体途径介导的细胞凋亡在兔颅内动脉瘤生成中的作用[J]. 中国脑血管病杂志, 2015,12(1):32-36.
[13] Shoshan-Barmatz V, De Pinto V, Zweckstetter M, et al. VDAC, a multi-functional mitochondrial protein regulating cell Life and death[J]. Mol Aspects Med, 2010, 31(3):227-285.
[14] Park E, Lee G J, Choi S, et al. The role of glutamate release on voltage-dependent anion channels (VDAC)-mediated apoptosis in an eleven vessel occlusion model in rats[J]. PLoS One, 2010, 5(12):e15192.
[15] Yang M, Camara A K, Wakim B T, et al. Tyrosine nitration of voltage-dependent anion channels in cardiac ischemia-reperfusion:reduction by peroxynitrite scavenging[J].Biochim Biophys Acta, 2012, 1817(11):2049-2059.
[16] Yu Z, Liu N, Li Y, et al. Neuroglobin overexpression inhibits oxygen-glucose deprivation-induced mitochondrial permeability transition pore opening in primary cultured mouse cortical neurons[J]. Neurobiol Dis, 2013, 56:95-103.
[17] Ren R, Zhang Y, Li B, et al. Effect of β-amyloid (25-35) on mitochondrial function and expression of mitochondrial permeability transition pore proteins in rat hippocampal neurons[J]. J Cell Biochem, 2011, 112(5):1450-1457.
[18] Matsumura M, Tsuchida M, Lsoyama N, et al. FTY720 mediates cytochrome c release from mitochondria during rat thymocyte apoptosis[J]. Transpl Immunol, 2010, 23(4):174-179.
[19] Eloy L, Jarrousse A S, Teyssot M L, et al. Anticancer activity of silver-N-heterocyclic carbene complexes:caspase-independent induction of apoptosis via mitochondrial apoptosis-inducing factor (AIF)[J]. Chem Med Chem, 2012, 7(5):805-815.
[20] Sun L, Strelow H, Mies G, et al. Oxygen therapy improves energy metabolism in focal cerebral ischemia[J]. Brain Res, 2011,1415(1):103-108.

常压高浓度氧下调电压依赖性阴离子通道蛋白对脑缺血-再灌注损伤大鼠的保护作用

Normobaric hyperoxia protect cerebral ischemia/reperfusion injured rats by downregulating voltage-dependent anion channel protein

PDF

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	张莹, 刘超楠, 时红林, 刘芳, 陈德喜, 时红波. P53凋亡刺激蛋白2介导酒精性肝病脂代谢相关基因的转录组学分析[J]. 首都医科大学学报, 2023, 44(1): 85-92.
[2]	刘志斌, 靳松, 牛亦农. 苯乙基异硫氰酸酯对良性前列腺上皮细胞增殖凋亡的影响及相关机制研究[J]. 首都医科大学学报, 2021, 42(6): 961-966.
[3]	安松林, 马玲, 赵月, 李雁. 主要促进因子超家族成员MFSD2A对肝癌细胞增殖、凋亡和侵袭的影响[J]. 首都医科大学学报, 2021, 42(6): 1000-1006.
[4]	崔兴, 钟萍. 我的梦想是做“百年老店”——记首都医科大学三博脑科医院神经外科于春江教授[J]. 首都医科大学学报, 2021, 42(1): 167-169.
[5]	刘妍, 陈玉静, 陈文强, 黄小波. 远志汤对慢性脑低灌注大鼠认知功能及海马凋亡蛋白的影响[J]. 首都医科大学学报, 2019, 40(3): 323-329.
[6]	张怡尘, 曹曦, 杨金奎. G蛋白偶联受体MAS对肝脏糖脂代谢的影响[J]. 首都医科大学学报, 2019, 40(3): 409-416.
[7]	卢晶, 沈涵, 程呈, 刘敬怡, 朱晓蓉, 谢荣荣, 袁明霞, 杨金奎. 人ether-α-go-go钾通道减少肝脏的内质网应激和凋亡[J]. 首都医科大学学报, 2019, 40(1): 45-52.
[8]	师文娟, 赵咏梅, 戚智锋, 黄语悠, 房亚兰, 刘克建. 常压高浓度氧对脑缺血-再灌注大鼠缺血核心区核转录因子-κB的适度调节作用[J]. 首都医科大学学报, 2018, 39(3): 349-354.
[9]	宋丽妮, 曹曦, 刘薇, 杨金奎. 血管紧张素转化酶2对肝细胞凋亡的影响[J]. 首都医科大学学报, 2018, 39(2): 223-229.
[10]	金双, 高连印, 赵梦培, 车念聪, 张秋云, 杜宇琼. 清毒汤对实验性重症肝损伤大鼠Bax蛋白及Bcl-2蛋白表达的影响[J]. 首都医科大学学报, 2018, 39(1): 79-83.
[11]	彭世光, 李娜, 蓝祖连, 李莉, 何焱玲. 早幼粒白血病在银屑病病人外周血淋巴细胞中的表达及其与p53和bcl-2家族的相关性[J]. 首都医科大学学报, 2017, 38(5): 645-649.
[12]	郭轶先, 张蓝方, 孙雪静, 万岁桂, 夏长青. 紫外线照射未成熟树突状细胞诱导小鼠同种抗原免疫耐受及其机制研究[J]. 首都医科大学学报, 2017, 38(3): 431-438.
[13]	史婷婷, 杨芳远, 曹曦, 卢晶, 谢荣荣, 袁明霞, 杨金奎. 血管紧张素转化酶2减少胰岛细胞的氧化应激及凋亡[J]. 首都医科大学学报, 2017, 38(2): 151-155.
[14]	穆凌云, 李金霞, 张秋云, 陈煜, 高连印, 杜宇琼. 截断逆挽方对慢加急性肝衰竭模型大鼠血清TNF-α、肝组织p-JNK及c-Jun的影响[J]. 首都医科大学学报, 2017, 38(2): 282-288.
[15]	杨巍巍, 李旭冉, 李昕, 李旭颖, 于顺. 脑血红蛋白表达增高可减轻α-突触核蛋白引起的MES23.5细胞凋亡[J]. 首都医科大学学报, 2016, 37(6): 799-805.