[1]许伟,朱继.液态氟碳纳米粒在大鼠蛛网膜下腔出血中对低氧诱导因子1α的抑制作用[J].第三军医大学学报,2016,38(03):251-257.
 Xu Wei,Zhu Ji.Perfluorooctyl-bromide nanoparticles inhibit hypoxia-inducible factor 1α in early brain injury of rats after subarachnoid hemorrhage[J].J Third Mil Med Univ,2016,38(03):251-257.
点击复制

液态氟碳纳米粒在大鼠蛛网膜下腔出血中对低氧诱导因子1α的抑制作用(/HTML )
分享到:

《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
38卷
期数:
2016年第03期
页码:
251-257
栏目:
基础医学
出版日期:
2016-02-15

文章信息/Info

Title:
Perfluorooctyl-bromide nanoparticles inhibit hypoxia-inducible factor 1α in early brain injury of rats after subarachnoid hemorrhage
作者:
许伟朱继
重庆医科大学附属第一医院神经外科
Author(s):
Xu Wei Zhu Ji

Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

关键词:
蛛网膜下腔出血早期脑损伤液态氟碳纳米粒低氧诱导因子1&alpha
Keywords:
subarachnoid hemorrhage early brain injury perfluorooctyl-bromide nanoparticles  hypoxia-inducible factor 1&alpha
分类号:
R743.35; R965; R979.9
文献标志码:
A
摘要:

目的      初步探讨液态氟碳(perfluorooctyl-bromide,PFOB)纳米粒对蛛网膜下腔出血后早期脑损的保护作用及其与低氧诱导因子1α(HIF-1α)的关系。      方法      健康雄性SD大鼠100只分为5个组:假手术组(Sham)、蛛血组(SAH)、蛛血+安慰剂组(SAH+vehicle)、蛛血+5 g/kg PFOB组(SAH+5 g/kg PFOB)和蛛血+10 g/kg PFOB组(SAH+10 g/kg PFOB),每组20只。采用颈内动脉穿刺法制作SAH模型。造模后24 h对每组大鼠进行神经行为功能缺损评分,检测脑含水量和血脑屏障(BBB)通透性,末端脱氧核苷酸介导的X-dUTP缺口末端标记法(TUNEL)检测神经元凋亡,免疫组化和Western blot检测HIF-1α蛋白表达情况。      结果      PFOB纳米粒能够显著降低早期脑损伤,包括改善神经功能缺失、减轻脑水肿、降低血脑屏障通透性和减少神经元凋亡,且SAH+10 g/kg PFOB组降低效果明显高于SAH+5 g/kg PFOB组(P<0.05)。PFOB在降低早期脑损伤的同时能够显著抑制HIF-1α蛋白表达,且SAH+10 g/kg PFOB组抑制效果明显高于SAH+5 g/kg PFOB组(P<0.05)。      结论      液态氟碳纳米粒对蛛网膜下腔出血后早期脑损伤的保护作用可能与抑制HIF-1α蛋白表达有关。

Abstract:

Objective       To determine the protective effect of perfluorooctyl-bromide (PFOB) nanoparticles on the early brain injury (EBI) in rats after subarachnoid hemorrhage (SAH) and its relationship with hypoxia-inducible factor 1 alpha (HIF-1α).       Methods       A total of 100 healthy male Sprague Dawley rats were randomly divided into 5 groups, that is, sham-operation, SAH, SAH+vehicle, SAH+5 mg/kg PFOB and SAH+10 mg/kg PFOB, with 20 animals in each group. Rat SAH model was established by endovascular perforation, and PFOB treatment (injected through the caudal vein) was initiated in 1 h after SAH. After their neurobehavioral function was evaluated in 24 h after surgery, all rats were subsequently sacrificed to detect brain water content and the blood-brain barrier (BBB) permeability. TUNEL staining was used to detect neural apoptosis, immunohistochemical assay and Western blotting to detect HIF-1α expression.       Results       PFOB treatment significantly alleviated EBI, including neurological dysfunction, brain edema, blood-brain barrier disruption and neural cell apoptosis, with the high-dose group more obvious (P<0.05). In addition, it also suppressed the expression of HIF-1α in the rat hippocampus. The effects of 10 g/kg PFOB were more obvious than those of 5 g/kg PFOB (P<0.05).       Conclusion       PFOB alleviates EBI after SAH, potentially through down-regulation of HIF-1α.

参考文献/References:

[1]Connolly E S Jr, Rabinstein A A, Carhuapoma J R, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage:  a guideline for healthcare professionals from the American Heart Association/American Stroke Association[J]. Stroke, 2012, 43(6):  1711-1737. DOI: 10.1161/STR.0b013e3182587839
[2]Cahill W J, Calvert J H, Zhang J H. Mechanisms of early brain injury after subarachnoid hemorrhage[J]. J Cereb Blood Flow Metab, 2006, 26(11):  1341-1353. DOI: 10.1038/sj.jcbfm.9600283
[3]Kusaka G, Ishikawa M, Nanda A, et al. Signaling pathways for early brain injury after subarachnoid hemorrhage[J]. J Cereb Blood Flow Metab, 2004, 24(8):  916-925. DOI: 10.1097/01.WCB.0000125886.48838.7E
[4]Sehba F A, Bederson J B. Mechanisms of acute brain injury after subarachnoid hemorrhage[J]. Neurol Res, 2006, 28(4):  381-398.  DOI: 10.1179/016164106X114991
[5]Semenza G L, Agani F, Feldser D, et al. Hypoxia, HIF-1, and the pathophysiologi of common human diseases[J]. Adv Exp Med Biol, 2000, 475:  123-130.
[6]Ostrowski R P, Colohan A R, Zhang J H. Mechanisms of hyperbaric oxygen-induced neuroprotection in a rat model of subarachnoid hemorrhage[J]. J Cereb Blood Flow Metab, 2005, 25(5):  554-571. DOI: 10.1038/sj.jcbfm.9600048
[7]Yan J, Chen C, Lei J, et al. 2-methoxyestradiol reduces cerebral vasospasm after 48 hours of experimental subarachnoid hemorrhage in rats[J]. Exp Neurol, 2006, 202(2):  348-356. DOI: 10.1016/j.expneurol.2006.06.009
[8]Wang Z, Meng C J, Shen X M, et al. Potential contribution of hypoxia-inducible factor-1α, aquaporin-4, and matrix metalloproteinase-9 to blood-brain barrier disruption and brain edema after experimental subarachnoid hemorrhage[J]. J Mol Neurosci, 2012, 48(1):  273-280. DOI: 10.1007/s12031-012-9769-6
[9]Hishikawa T, Ono S, Ogawa T, et al. Effect of deferoxamine-activated hypoxia inducible factor-1 on the brainstem following subarachnoid haemorrhage[J]. Neurosurgery, 2008, 62(1): 232-241. DOI: 10.1227/01.NEU.0000311082.88766.33
[10]Wu C, Hu Q, Chen J, et al. Inhibiting HIF-1α by 2ME2 ameliorates early brain injury after experimental subarachnoid hemorrhage in rats[J]. Biochem Biophys Res Commun, 2013, 437(3):  469-474. DOI: 10.1016/j.bbrc.2013.06.107
[11]Lin C Y, Javadi M, Belnap D M, et al. Ultrasound sensitive eLiposomes containing doxorubicin for drug targeting therapy[J]. Nanomedicine, 2014, 10(1):  67-76. DOI: 10.1016/j.nano.2013.06.011
[12]Chen J, Pan H, Lanza G M, et al. Perfluorocarbon nanoparticles for physiological  and molecular imaging and therapy[J]. Adv Chronic Kidney Dis, 2013, 20(6):  466-478. DOI: 10.1053/j.ackd.2013.08.004
[13]Kaneda M M, Caruthers S, Lanza G M, et al. Perfluorocarbon nanoemulsions for quantitative molecular imaging and targeted therapeutics[J]. Ann Biomed Eng, 2009, 37(10):  1922-1933. DOI: 10.1007/s10439-009-9643-z
[14]Zhang H, Xu R, Xie F, et al. Protective effects of perfluorooctyl-bromide nanoparticles on early brain injuries following subarachnoid hemorrhage in rats[J]. Am J Transl Res, 2015, 7(8):  1404-1416.
[15]Veelken J A, Laing R J, Jakubowski J. The Sheffield model of subarachnoid hemorrhage in rats[J]. Stroke, 1995, 26(7):  1279-1284.
[16]Bederson J B, Germano I M, Guarino L. Cortical blood flow and cerebral perfusion pressure in a new noncraniotomy model of subarachnoid hemorrhage in the rat[J]. Stroke, 1995, 26(6):  1086-1092.
[17]Yamaguchi M, Zhou C, Nanda A, et al. Ras protein contributes to cerebral vasospasm in a canine double-hemorrhage model[J]. Stroke, 2004, 35(7):  1750-1755. DOI: 10.1161/01.STR.0000129898.68350.9f
[18]Semenza G L, Wang G L. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation[J]. Mol Cell Biol, 1992, 12(12):  5447-5454.
[19]Higashida T, Kreipke C W, Rafols J A, et al. The role of hypoxia-inducible factor-1α, aquaporin-4, and matrix metalloproteinase-9 in blood-brain barrier disruption and brain edema after traumatic brain injury[J]. J Neurosurg, 2011, 114(1):  92-101. DOI: 10.3171/2010.6.JNS10207
[20]Chen C, Hu Q, Yan J, et al. Early inhibition of HIF-1α with small interfering RNA reduces ischemic-reperfused brain injury in rats[J]. Neurobiol Dis, 2009, 33(3):  509-517. DOI: 10.1016/j.nbd.2008.12.010
[21]胡强, 吴骋, 陈敬寅, 等. 蛛网膜下腔出血大鼠早期大脑皮层低氧诱导因子-1α 表达与细胞凋亡相关性研究[J]. 浙江大学学报:  医学版, 2014, 43(1):  58-65.
[22]Augustin A J, Spitznas M, Koch F, et al. Effects of perfluorooctylbromide and vitamin E on ischemia induced retinal oxidative tissue damage[J]. Exp Eye Res 1998, 66(1):  19-24.
[23]Rotta A T, Gunnarsson B, Fuhrman B P, et al. Perfluorooctyl bromide (perflubron) attenuates oxidative injury to biological and nonbiological systems[J]. Pediatr Crit Care Med, 2003, 4(2):  233-238.
[24]Zhou Z, Sun D, Levasseur J E, et al. Perfluorocarbon emulsions improve cognitive recovery after lateral fluid percussion brain injury in rats[J]. Neurosurgery, 2008, 63(4):  799-807. DOI: 10.1227/01.NEU.0000325493.51900.53
[25]Yacoub A, Hajec M C, Stanger R, et al. Neuroprotective effects of perflurocarbon (oxycyte) after contusive spinal cord injury[J]. J Neurotrauma, 2014, 31(3):  256-267. DOI: 10.1089/neu.2013.3037

相似文献/References:

[1]张桓,朱继.液态氟碳纳米粒对大鼠蛛网膜下腔出血后早期脑损伤的保护作用[J].第三军医大学学报,2015,37(18):1842.
 Zhang Huan,Zhu Ji.Perfluorooctyl-bromide nanoparticles protect early brain injury in rats after sub-arachnoid hemorrhage[J].J Third Mil Med Univ,2015,37(03):1842.
[2]陈佳琳,姚声涛,郭宗铎.TNF-α在实验性蛛网膜下腔出血后早期脑损伤中的作用[J].第三军医大学学报,2011,33(15):1620.
 Chen Jialin,Yao Shengtao,Guo Zongduo.Role of TNF-α in early brain injury after subarachnoid hemorrhage in rats[J].J Third Mil Med Univ,2011,33(03):1620.
[3]雷波,谢宗义,马颖,等.大鼠蛛网膜下腔出血后皮质中VDAC1的表达与神经元凋亡的关系[J].第三军医大学学报,2011,33(16):1705.
 Lei Bo,Xie Zongyi,Ma Ying,et al.Correlation between VDAC1 expression and neuronal apoptosis in cerebral cortex of rats in early brain injury after subarachnoid hemorrhage[J].J Third Mil Med Univ,2011,33(03):1705.
[4]陈佳琳,姚声涛,陈良勇,等.米诺环素对大鼠蛛网膜下腔出血后早期脑损伤的保护作用[J].第三军医大学学报,2010,32(17):1847.
 Chen Jialin,Yao Shengtao,Chen Liangyong,et al.Effect of minocycline on early brain injury after subarachnoid hemorrhage in rats[J].J Third Mil Med Univ,2010,32(03):1847.
[5]林斌,孙晓川,张晓冬,等.APOE基因多态性与动脉瘤性蛛网膜下腔出血后早期脑功能改变的相关性[J].第三军医大学学报,2010,32(07):700.
 Lin Bin,Sun Xiaochuan,Zhang Xiaodong,et al.Association between APOE polymorphism and brain function in early stage of aneurysmal subarachnoid hemorrhage[J].J Third Mil Med Univ,2010,32(03):700.
[6]郭宗铎,孙晓川,何朝晖,等.蛛网膜下腔出血后早期海马MMP-9的表达与海马神经元凋亡的相关性研究[J].第三军医大学学报,2009,31(01):71.
 GUO Zong-duo,SUN Xiao-chuan,HE Zhao-hui,et al.Association between hippocampal MMP-9 expression and neuronal apoptosis in early brain injury in rats after subarachnoid hemorrhage[J].J Third Mil Med Univ,2009,31(03):71.
[7]张光伟,贺学农,周昌龙,等.血小板源性生长因子受体在实验性蛛网膜下腔出血后早期脑损伤中的作用[J].第三军医大学学报,2013,35(13):1398.
 Zhang Guangwei,He Xuenong,Zhou Changlong,et al.Role of platelet-derived growth factor receptor in early brain injury following subarachnoid hemorrhage[J].J Third Mil Med Univ,2013,35(03):1398.
[8]张红霞,蒋登志,车旭东,等.依布硒林减轻DMT1诱导的铁死亡在实验性大鼠蛛网膜下腔出血中的研究[J].第三军医大学学报,2017,39(16):1618.
 ZHANG Hongxia,JIANG Dengzhi,CHE Xudong,et al.Ebselen relieves ferroptosis induced by divalent mental transporter 1 in rats with subarachnoid hemorrhage[J].J Third Mil Med Univ,2017,39(03):1618.
[9]黎新慎,彭建华,庞金伟,等.载脂蛋白E拟肽COG1410对蛛网膜下腔出血后自噬和凋亡的影响[J].第三军医大学学报,2017,39(24):2366.
 LI Xinshen,PENG Jianhua,PANG Jinwei,et al.Effects of apolipoprotein E mimetic peptide COG1410 on central autophagy and apoptosis after subarachnoid hemorrhage in mice[J].J Third Mil Med Univ,2017,39(03):2366.
[10]梁译丹,覃王,黄豪,等.自噬通过降解铁蛋白促进神经元铁死亡参与蛛网膜下腔出血后早期脑损伤[J].第三军医大学学报,2019,41(15):1407.
 LIANG Yidan,QIN Wang,HUANG Hao,et al.Autophagy promotes neuronal ferroptosis by degrading ferritin and induces early brain injury after subarachnoid hemorrhage in rats[J].J Third Mil Med Univ,2019,41(03):1407.

更新日期/Last Update: 2016-01-27