[1]张璐璐,朱欣茹,李文强,等.核转录因子 E2 相关因子 2对脑缺血再灌注大鼠脑组织中炎症因子表达和神经胶质细胞活化的影响[J].新乡医学院学报,2020,37(4):301-305.[doi:10.7683/xxyxyxb.2020.04.001]
 ZHANG Lulu,ZHU Xinru,LI Wenqiang,et al.Expression of nuclear factor erythroid 2-related factor in the brain of ischemia-reperfusion rats and the effect of it′s over expression on the activation of inflammatory factors and neuroglial cells[J].Journal of Xinxiang Medical University,2020,37(4):301-305.[doi:10.7683/xxyxyxb.2020.04.001]
点击复制

核转录因子 E2 相关因子 2对脑缺血再灌注大鼠脑组织中炎症因子表达和神经胶质细胞活化的影响
分享到:

《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
37
期数:
2020年4
页码:
301-305
栏目:
基础研究
出版日期:
2020-04-05

文章信息/Info

Title:
Expression of nuclear factor erythroid 2-related factor in the brain of ischemia-reperfusion rats and the effect of it′s over expression on the activation of inflammatory factors and neuroglial cells
作者:
张璐璐1朱欣茹1李文强1张朝辉1宋景贵2
(1.新乡医学院第二附属医院,河南 新乡 453002;2.新乡医学院第一附属医院,河南 卫辉 453100)
Author(s):
ZHANG Lulu1ZHU Xinru1LI Wenqiang1ZHANG Zhaohui1SONG Jinggui2
(1.The Second Affiliated Hospital of Xinxiang Medical University;Xinxiang 453002,Henan Province,China;2.The First Affiliated Hospital of Xinxiang Medical University,Weihui 453100,Henan Province,China )
关键词:
核转录因子 E2 相关因子 2脑缺血再灌注炎症因子小胶质细胞星形胶质细胞
Keywords:
nuclear factor erythroid 2-related factorischemia-reperfusioninflammatory factorsmicrogliaastrocytes
分类号:
R743.3
DOI:
10.7683/xxyxyxb.2020.04.001
文献标志码:
A
摘要:
目的 探讨核转录因子 E2 相关因子 2(Nrf 2)在脑缺血再灌注大鼠脑组织中的表达及其对缺血再灌注所引起的炎症反应及神经胶质细胞活化标志物表达的影响。方法 30只雄性Sprague Dawley大鼠随机分为正常组、假手术组、卒中梗阻侧组、卒中梗阻对侧组、Nrf 2激动剂组及空白溶剂组,每组5只。正常组大鼠不给予任何干预措施,假手术组大鼠行皮肤切开缝合术,卒中梗阻侧组、卒中梗阻对侧组、Nrf 2激动剂组、空白溶剂组大鼠行大脑中动脉栓塞术制备缺血性脑卒中模型。造模手术后Nrf 2激动剂组、空白溶剂组大鼠分别经尾静脉注射0.1 mL 特丁基对苯二酚和 0.1 mL 生理盐水。手术后3 d取大鼠脑组织,采用Western blot法检测正常组、假手术组、卒中梗阻侧组、卒中梗阻对侧组大鼠脑组织中炎症因子白细胞介素-6(IL-6)和干扰素(IFN)蛋白的表达,检测假手术组、卒中梗阻侧组和Nrf 2激动剂组大鼠脑组织中Nrf 2蛋白表达,检测正常组、假手术组、卒中梗阻侧组、Nrf 2激动剂组、空白溶剂组大鼠脑组织中IL-6、IFN、小胶质细胞活化标志物离子钙结合衔接分子1(Iba-1)、星形胶质细胞活化标志物胶质原纤维酸性蛋白(GFAP)的表达。结果 假手术组、卒中梗阻对侧组及正常组大鼠脑组织中IFN、IL-6蛋白表达比较差异均无统计学意义(P>0.05),卒中梗阻侧组大鼠脑组织中IFN、IL-6蛋白表达高于正常组、假手术组和卒中梗阻对侧组(P<0.05)。卒中梗阻侧组大鼠脑组织中Nrf 2蛋白表达高于假手术组(P<0.05),Nrf 2激动剂组大鼠脑组织中Nrf 2蛋白表达高于假手术组、卒中梗阻侧组(P<0.05)。正常组、假手术组及Nrf 2激动剂组大鼠脑组织中IFN、IL-6、Iba-1、GFAP蛋白表达比较差异均无统计学意义(P>0.05),卒中梗阻侧组与空白溶剂组大鼠脑组织中IFN、IL-6、Iba-1、GFAP蛋白表达比较差异无统计学意义(P>0.05),正常组、假手术组及Nrf 2激动剂组大鼠脑组织中IFN、IL-6、Iba-1、GFAP蛋白表达低于卒中梗阻侧组、空白溶剂组(P<0.05)。结论 脑缺血再灌注可诱导中枢神经系统发生炎症反应,Nrf 2在脑缺血再灌注大鼠脑组织中表达上调, Nrf 2过表达可通过激活Nrf 2/ARE 通路而抑制神经胶质细胞活化标志物的表达,降低炎症反应水平,改善脑组织缺血再灌注损伤。
Abstract:
Objective To investigate the expression of nuclear factor erythroid 2-related factor(Nrf 2) in the brain of ischemia-reperfusion rats and the effect of Nrf 2 overexpression on the inflammatory factors and activation markers of neuroglial cells.Methods Thirty male Sprague Dawley rats were randomly divided into normal group,sham operation group,stroke side group,stroke contralateral group,Nrf 2 activation group and blank solvent group,with five rats in each group.The rats in the normal group did not give any intervention;the rats in the sham operation group were treated with skin incision and suture; the rats in the stroke side group,stroke contralateral group,Nrf 2 activation group and blank solvent group were given middle cerebral artery occlusion operation to prepare ischemic stroke model.After modelling,the rats in the Nrf 2 activation group and blank solvent group were treated with 0.1 mL tertiary butylhydroquinone and 0.1 mL normal saline by caudal vein injection respectively.The brain tissue of rats was taken at 3 d after operation,and the expression of interleukin-6 (IL-6) and interferon (IFN) in brain tissue of rats were detected by Western blot in normal group,sham operation group,stroke side group and stroke contralateral group;the expression of Nrf 2 in brain tissue of rats was detected by Western blot in sham operation group,stroke side group,Nrf 2 activation group;the expression of IL-6,IFN,activation markers of lionized calcium binding adaptor molecule 1 (Iba-1) of microglia and glial fibrillary acidic protein (GFAP) of astrocytes in brain tissue of rats were detected by Western blot in normal group,sham operation group,stroke side group,Nrf 2 activation group and blank solvent group.Results There was no significant difference in the expression of IL-6,IFN among the sham operation group,stroke contralateral group and normal group(P>0.05);the expression of IL-6,IFN in brain tissue of rats in the stroke side group were significantly higher than those in the normal group,sham operation group and stroke contralateral group(P<0.05).The expression of Nrf 2 protein in brain tissue of rats in the stroke side group was significantly higher than that in the sham operation group(P<0.05);the expression of Nrf 2 protein in brain tissue of rats in the Nrf 2 activation group was significantly higher than that in the sham operation group and stroke side group(P<0.05).There was no significant difference in the expression of IL-6,IFN,Iba-1,GFAP protein among the normal group,sham operation group,Nrf 2 activation group(P>0.05);there was no significant difference in the expression of IL-6,IFN,Iba-1,GFAP protein between the stroke side group and blank solvent group(P>0.05);the expressions of IL-6,IFN,Iba-1,GFAP protein in brain tissue of rats in the normal group,sham operation group,Nrf 2 activation group were significantly lower than those in the stroke side group,blank solvent group(P<0.05).Conclusion Ischemia-reperfusion can induce inflammation reaction of the central nervous system.The expression of Nrf 2,a key factor regulating cellular inflammatory response,is elevated in ischemia-reperfusion rats.The overexpression Nrf 2 can activate the Nrf 2/ARE pathway through,so then inhibit the expression of activation markers of glial cells in brain tissue,reduce inflammation level,and improve the ischemia-reperfusion injury of brain tissue.

参考文献/References:

[1] IADECOLA C,ANRATHER J.The immunology of stroke:from mechanisms to translation[J].Nat Med,2011,17(7):796-808.
[2] MEYER S F,DENORME F,LANGHAUSER F,et al.Thromboinflammation in stroke brain damage[J].Stroke,2016,47(4):1165-1172.
[3] PETROVIC D D,GOONEWARDENA S N,PINSKY D J.Inflammatory disequilibrium in stroke[J].Circ Res,2016,119(1):142-158.
[4] CANDELARIO J E,ARMANDO G F,MICHEL G C,et al.Post-ischaemic treatment with the cyclooxygenase-2 inhibitor nimesulide reduces blood-brain barrier disruption and leukocyte infiltration following transient focal cerebral ischaemia in rats[J].J Neurochem,2007,100(4):1108-1120.
[5] MURGAS P,GODOY B,BEMHARDI R V.Aβ potentiates inflammatory activation of glial cells induced by scavenger receptor ligands and inflammatory mediators in culture[J].Neurotox Res,2012,22(1):69-78.
[6] MORI T,K0YAMA N,ARENDASH G W,et al.Overexpression of human S100B exacerbates cerebral amyloidosis and gliosis in the Tg2576 mouse model of Alzheimer′s disease[J].Glia,2010,58(3):300-314.
[7] KUNDU J K,SURH Y J.Nrf 2-Keap1 signaling as a potential target for chemoprevention of inflammation-associated carcinogenesis[J].Pharm Res,2010,27(6):999-1013.
[8] SINGH S,VRISHNI S,SINGH B K,et al.Nrf 2-ARE stress response mechanism:a control point in oxidative stress-mediated dysfunctions and chronic inflammatory diseases[J].Free Radic Res,2010,44(11):1267-1288.
[9] INNAMORATO N G,ROJO A I,GARCIA-YAGUE A J,et al.The transcription factor Nrf 2 is a therapeutic target against brain inflammation[J].J Immunol,2008, 181(1):680-689.
[10] TANAKA N,IKEDA Y,OHTA Y,et al.Expression of Keap1- Nrf 2 system and antioxidative proteins in mouse brain after transient middle cerebral artery occlusion[J].Brain Res,2011,1370:246-253.
[11] YANG Y C,LI C K,WEI Y L,et al.Docosahexaenoic acid inhibition of inflammation is partially via cross-talk between Nrf 2/heme oxygenase 1 and IKK/NF-κB pathways[J].Nutr Biochem,2013,24(1):204-212.
[12] CHANG C Y,KUAN Y H,LI J R,et al.Docosahexaenoic acid reduces cellular inflammatory response following permanent focal cerebral ischemia in rats[J].Nutr Biochem,2013,24(12):2127-2137.
[13] PURDOM-DICKINSON S E,LIN Y,DEDEK M,et al.Induction of antioxidant and detoxification response by oxidants in cardiomyocytes:evidence from gene expression profiling and activation of Nrf 2 transcription factor[J].J Mol Cell Cardiol,2007,42(1):159-176.
[14] 张莹,卢艺,曹旭,等.Nrf 2在短暂性缺血再灌注大鼠星形胶质细胞模型中的表达变化及其意义[J].中风与神经疾病杂志,2010,27(5):388-391.

相似文献/References:

[1]赵红岗 李东亮,王东霞 祈英杰,周素凤,等.黄体酮对大鼠脑缺血区水和钠钾钙含量的影响[J].新乡医学院学报,2000,17(02):077.
[2]乔建新,刘熙鹏,刘 明,等.加贝酯对脑缺血再灌注大鼠脑组织病理学改变的影响[J].新乡医学院学报,2021,38(3):226.[doi:10.7683/xxyxyxb.2021.03.005]
 QIAO Jianxin,LIU Xipeng,LIU Ming,et al.Effect of gabexate mesilate on pathological changes of brain tissue of rats with cerebral ischemia reperfusion[J].Journal of Xinxiang Medical University,2021,38(4):226.[doi:10.7683/xxyxyxb.2021.03.005]
[3]李 青,白宏英,徐志秀,等.乌司他丁对脑缺血再灌注大鼠脑组织中基质金属蛋白酶-9活性和细胞外基质表达的影响[J].新乡医学院学报,2020,37(10):912.[doi:10.7683/xxyxyxb.2020.10.003]
 LI Qing,BAI Hongying,XU Zhixiu,et al.Effect of ulinastatin on the activity of matrix metalloproteinase-9 and the expression of extracellular matrix in brain tissues of rats with cerebral ischemia-reperfusion[J].Journal of Xinxiang Medical University,2020,37(4):912.[doi:10.7683/xxyxyxb.2020.10.003]
[4]赵 欣,裴科阳,谭 军.腺苷预处理对大鼠局灶性脑缺血再灌注后线粒体活性氧含量及线粒体呼吸链复合体Ⅰ、Ⅲ活性和脑组织总抗氧化能力的影响[J].新乡医学院学报,2019,36(4):305.[doi:10.7683/xxyxyxb.2019.04.002]
 ZHAO Xin,PEI Ke-yang,TAN Jun.Effect of adenosine preconditioning on reactive oxygen species content,activity of respiratory chain complex Ⅰ and Ⅲ of mitochondria and the total antioxidant capacity of brain tissueafter focal cerebral ischemia-reperfusion in rats[J].Journal of Xinxiang Medical University,2019,36(4):305.[doi:10.7683/xxyxyxb.2019.04.002]
[5]王文杰,左 霞,郭俐宏,等.大株红景天注射液对大鼠脑缺血再灌注后血管内皮损伤的影响[J].新乡医学院学报,2016,33(1):026.[doi:10.7683/xxyxyxb.2016.01.008]
 WANG Wen-Jie,ZUO Xia,GUO Li-hong,et al.Effect of rhodiola kirilowii Regel injection on rats with vascular endothelial induced by cerebral ischemia reperfusion[J].Journal of Xinxiang Medical University,2016,33(4):026.[doi:10.7683/xxyxyxb.2016.01.008]

更新日期/Last Update: 2020-04-05