NF-κB和Nrf2在DHA拮抗1-溴丙烷中枢神经毒性中的作用

doi:10.6040/j.issn.1671-7554.0.2015.791

山东大学学报（医学版） ›› 2016, Vol. 54 ›› Issue (4): 84-88.doi: 10.6040/j.issn.1671-7554.0.2015.791

NF-κB和Nrf2在DHA拮抗1-溴丙烷中枢神经毒性中的作用

王增金,袁华,杨俊林,谢克勤,赵秀兰

山东大学公共卫生学院毒理学系, 山东济南 250012

收稿日期:2015-08-20 出版日期:2016-04-10 发布日期:2016-04-10
通讯作者: 赵秀兰. E-mail: zhao.xl@sdu.edu.cn E-mail:zhao.xl@sdu.edu.cn
基金资助:
国家自然科学基金(81172708);山东省科技攻关计划课题(2011GSF11814)

DHA attenuated central neurotoxicity of 1-bromopropane by activating NF-κB and Nrf2

WANG Zengjin, YUAN Hua, YANG Junlin, XIE Keqin, ZHAO Xiulan

Department of Toxicology, School of Public Health, Shandong University, Jinan 250012, Shandong, China

Received:2015-08-20 Online:2016-04-10 Published:2016-04-10

摘要/Abstract

摘要： 目的观察核因子-κB(NF-κB)与NF-E2相关因子2(Nrf2)在DHA拮抗1-溴丙烷(1-BP)中枢神经毒性中的作用。方法 48只Wistar大鼠随机分为对照组、1-BP组、250 mg/kg DHA+1-BP组(LDHA组)和500 mg/kgDHA+1-BP组(HDHA组)。各组动物均经口给予1-BP和DHA,连续12 d。Western blotting 和免疫荧光检测大脑前额叶皮层胞浆组分中NF-κB、Nrf2的激活、下游Ⅱ相酶的蛋白表达、大脑星形胶质细胞的激活及4-HNE氧化修饰蛋白质的变化。结果与对照组比较,1-BP组大脑胞浆和胞核中NF-κB、Nrf2的表达以及下游Ⅱ相酶的蛋白表达升高(P<0.05),与1-BP组相比,LDHA组和HDHA组NF-κB及Ⅱ相酶的蛋白表达降低(P<0.05),而Nrf2表达增加(P<0.05);与对照组比较,1-BP组星形胶质细胞激活数目增加,与1-BP组相比,LDHA组和HDHA组细胞激活数目减少; 1-BP组4-HNE修饰蛋白含量与对照组相比显著增加(P<0.05),与1-BP组比较,LDHA组和HDHA组4-HNE蛋白含量降低(P<0.05)。结论 DHA通过抑制NF-κB并且激活Nrf2,呈现对1-BP中枢神经毒性的拮抗作用。

关键词: 1-溴丙烷, 中枢神经毒性, 核因子-κB, NF-E2相关因子, 二十二碳六烯酸

Abstract: Objective To observe the role of nuclear factor-kappa B(NF-κB)and NF-E2-related factor 2(Nrf2)in DHA antagonizing central nervous system(CNS)neurotoxicity of 1-bromopropane(1-BP). Methods A total of 48 Wistar rats were randomly divided into control group, 1-BP group, 250 mg/kg DHA+1-BP group(LDHA group)and 500 mg/kg DHA+1-BP group(HDHA group). 1-BP and DHA were orally administered to all animals for 12 consecutive days. The prefrontal cortex cytoplasmic protein activation of NF-κB, Nrf2, phase II enzyme protein, activation of astrocyte and 4-hydroxy-2-nonenal(4-HNE)modified protein were measured with Western blotting and immunofluorescence. Results The cortex cytoplasmic and nuclear protein expressions of NF-κB, Nrf2 and phase II enzyme protein were significantly higher in the control group than in 1-BP group(P<0.05). Compared with the 1-BP group, the expression of NF-κB and II enzyme protein were significantly lower (P<0.05)but the level of Nrf2 was significantly higher in LDHA group and HDHA group(P<0.05). Compared with the control group, activated astrocytes in 1-BP group were significantly increased, while those in LDHA group and HDHA group were significantly decreased. The content of 4-HNE modified protein in 1-BP group was significantly higher than in the control group(P<0.05). Compared with the 1-BP group, the content of 4-HNE modified protein was significantly lower in LDHA group and HDHA group(P<0.05). Conclusion DHA may show antagonism against CNS toxicity of 1-BP by inhibiting NF-κB and activating Nrf2. 山东大学学报 (医学版)54卷4期 -王增金,等.NF-κB和Nrf2在DHA拮抗1-溴丙烷中枢神经毒性中的作用 \=-

Key words: 1-bromopropane, Nuclear factor-kappa B, NF-E2-related factor 2, Docosahexaenoic acid, Central nervous system toxicity

中图分类号:

R994.6

王增金,袁华,杨俊林,谢克勤,赵秀兰. NF-κB和Nrf2在DHA拮抗1-溴丙烷中枢神经毒性中的作用[J]. 山东大学学报（医学版）, 2016, 54(4): 84-88.

WANG Zengjin, YUAN Hua, YANG Junlin, XIE Keqin, ZHAO Xiulan. DHA attenuated central neurotoxicity of 1-bromopropane by activating NF-κB and Nrf2[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(4): 84-88.

参考文献

[1] 袁华, 张秀梅, 王清华, 等. 二十二碳六烯酸对1-溴丙烷致大鼠学习能力损伤的拮抗作用[J]. 环境与健康杂志, 2013, 30(8):668-671. YUAN Hua, ZHANG Xiumei, WANG Qinghua, et al. Antagonistic effect of docosahexaenoic acid on damaged learning ability induced by 1-bromopropane in rats[J]. Journal of Environment and Health, 2013, 30(8):668-671.
[2] Guo Y, Yuan H, Jiang L, et al. Involvement of decreased neuroglobin protein level in cognitive dysfunction induced by 1-bromopropane in rats[J]. Brain Research, 2015, 1600:1-16. doi:10.1016/j.brainres.2014.12.046.
[3] Yates CM, Calder PC, Ed Rainger G. Pharmacology and therapeutics of omega-3 polyunsaturated fatty acids in chronic inflammatory disease[J]. Pharmacol Ther, 2014, 141(3):272-282.
[4] Schwanke RC, Marcon R, Bento AF, et al. EPA- and DHA-derived resolvins’ actions in inflammatory bowel disease[J]. European J Pharmacol, 2015. doi:10.1016/j.ejphar.2015.08.050.
[5] Solbakk AK, Lovstad M. Effects of focal prefrontal cortex lesions on electrophysiological indices of executive attention and action control[J]. Scand J Psychol, 2014, 55(3):233-243.
[6] Zeng T, Zhang CL, Song FY, et al. PI3K/Akt pathway activation was involved in acute ethanol-induced fatty liver in mice[J]. Toxicology, 2012, 296(1-3):56-66.
[7] Gupta SC, Sundaram C, Reuter S, et al. Inhibiting NF-kappaB activation by small molecules as a therapeutic strategy[J]. Biochim Biophys Acta, 2010, 1799(10-12):775-787.
[8] Hirrlinger J, Dringen R. The cytosolic redox state of astrocytes: Maintenance, regulation and functional implications for metabolite trafficking[J]. Brain Res Rev, 2010, 63(1-2):177-188.
[9] Sofroniew MV, Vinters HV. Astrocytes: biology and pathology[J]. Acta Neuropathol, 2010, 119(1):7-35.
[10] Sofroniew MV. Molecular dissection of reactive astrogliosis and glial scar formation[J]. Trends Neurosci, 2009, 32(12):638-647.
[11] Lee E, Yin Z, Sidoryk-Wegrzynowicz M, et al. 15-Deoxy-Delta12,14-prostaglandin J(2)modulates manganese-induced activation of the NF-kappaB, Nrf2, and PI3K pathways in astrocytes[J]. Free Radic Biol Med, 2012, 52(6):1067-1074.
[12] Pettit LK, Varsanyi C, Tadros J, et al. Modulating the inflammatory properties of activated microglia with Docosahexaenoic acid and Aspirin[J]. Lipids Health Dis, 2013, 12:16. doi:10.1186/1476-511X-12-16.
[13] Cieslik M, Pyszko J, Strosznajder JB. Docosahexaenoic acid and tetracyclines as promising neuroprotective compounds with poly(ADP-ribose)polymerase inhibitory activities for oxidative/genotoxic stress treatment[J]. Neurochem Int, 2013, 62(5):626-636.
[14] Chitranjali T, Anoop Chandran P, Muraleedhara Kurup G. Omega-3 fatty acid concentrate from Dunaliella salina possesses anti-inflammatory properties including blockade of NF-kappaB nuclear translocation[J]. Immunopharmacol Immunotoxicol, 2015, 37(1):81-89.
[15] Pedruzzi LM, Stockler-Pinto MB, Leite M Jr, et al. Nrf2-keap1 system versus NF-κB: the good and the evil in chronic kidney disease?[J]. Biochimie, 2012, 94(12):2461-2466.
[16] Kim JH, Choi YK, Lee KS, et al. Functional dissection of Nrf2-dependent phase II genes in vascular inflammation and endotoxic injury using Keap1 siRNA[J]. Free Radic Biol Med, 2012, 53(3):629-640.
[17] Maniti O, Francois-Moutal L, Lecompte MF, et al. Protein “amyloid-like” networks at the phospholipid membrane formed by 4-hydroxy-2-nonenal-modified mitochondrial creatine kinase[J]. Mol Membr Biol, 2015, 32(1):1-10.
[18] Wakabayashi N, Slocum SL, Skoko JJ, et al. When NRF2 talks, who's listening?[J]. Antioxid Redox Signal, 2010, 13(11):1649-1663.
[19] Mao L, Wang H, Qiao L, et al. Disruption of Nrf2 enhances the upregulation of nuclear factor-kappaB activity, tumor necrosis factor-alpha, and matrix metalloproteinase-9 after spinal cord injury in mice[J]. Mediators Inflamm, 2010, 2010:238321. doi:10.1155/2010/238321.
[20] Jin W, Wang J, Zhu T, et al. Anti-inflammatory effects of curcumin in experimental spinal cord injury in rats[J]. Inflamm Res, 2014, 63(5):381-387.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed

NF-κB和Nrf2在DHA拮抗1-溴丙烷中枢神经毒性中的作用

DHA attenuated central neurotoxicity of 1-bromopropane by activating NF-κB and Nrf2

PDF (PC)

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 5

多维度评价

本文评价

推荐阅读 0

[1]	杨俊林,王清华,王增金,赵秀兰. 蛋白酶体活性升高在1-BP致大鼠周围神经损伤中的作用[J]. 山东大学学报（医学版）, 2016, 54(4): 78-83.
[2]	杨璐, 刘延国, 李际盛, 王秀问. 蟾毒灵对非小细胞肺癌顺铂化疗的增敏作用及机制[J]. 山东大学学报（医学版）, 2015, 53(3): 6-11.
[3]	刘粉叶,张继东,胡连海,来丽萍,杨发林 . 益肾活血胶囊对同型半胱氨酸致兔动脉粥样硬化MCP-1mRNA表达及NF-κB活化的影响[J]. 山东大学学报(医学版), 2008, 46(4): 353-356.
[4]	耿文静,柳方娥,焦波,程艳娜 . EPA、DHA对脂多糖诱导的大鼠系膜细胞增殖及凋亡的影响[J]. 山东大学学报(医学版), 2008, 46(1): 37-59.
[5]	肖迎,王琪,张效房,金学民,张金嵩 . GM-1对大鼠视网膜缺血再灌注损伤后NF-κB表达的影响[J]. 山东大学学报(医学版), 2007, 45(9): 910-913.