Protective Effect of Vitexin on Cerebral Ischemia-Reperfusion Injury in Rats

doi:10.3969/j.issn.2095-1396.2017.01.002

Abstract

Abstract: Objective：This study investigated the possible mechanism of vitexin in cerebral ischemia-reperfusion （CIR） model rats. Methods：Middle cerebral artery occlusion （MCAO） model was established in this study. This experiment was randomly divided into sham group，model group，model+edaravone group （3.24 μmol·kg-1），and different concentrations of vitexin groups （1.62，3.24，6.48 μmol·kg-1）. After 1 h of reperfusion，the rats were intraperitoneally injected for one and three days. Triphenyltetrazolium chloride （TTC） was used to measure brain infarct volume of rats，the water content of brain tissue was measured through wet-dry weighting method，methane dicarboxylic aldehyde （MDA） content，superoxide dismutase （SOD） activity and reactive oxygen species （ROS） were determined by kit methods，the positive cells of aquaporin-4 （AQP-4） were detected by immunohistochemistry，the mRNA levels of Tolllike receptor 4 （TLR4） and nuclear factor κB （NF-κB） mRNA were detected by RT-qPCR，tumor necrosis factor α（ TNF-α） content was measured by ELISA，the cell morphology of rats was observed by HE staining. Results：Compared to the sham group，model group showed significant
infarcts and increased brain water content. Compared to model group，vitexin decreased cerebral infarct volume and brain water content，increased SOD activity，and reduced the expressions of inflammatory factors significantly，improved cell morphology and the effects were dose dependent. Moreover，the protective effect of vitexin after 3 d treatment was better than that after 1 d. Compared to edaravone group，the effects of vitexin groups （1.62，3.24 μmol·kg-1） were lower （P<0.05，P<0.01），but showed similar effect of vitexin group at concentration of 6.48 μmol·kg-1. Conclusion：Vitexin could protect CIR injury through attenuating oxidative stress and inhibiting the inflammatory response.

Key words: vitexin, cerebral ischemia-reperfusion, antioxidation, anti-inflammation

CLC Number:

R965

DU Yun-guang，CAO Xin-xin，WANG Xiao-ru，WANG Shu-hua. Protective Effect of Vitexin on Cerebral Ischemia-Reperfusion Injury in Rats[J]. Acta Neuropharmacologica, 2017, 7(1): 10-23.

References

[1] Tang Xiang-jun, Yang Ming-huan, Cao Gang, et al. Protective effect of microRNA-138 against cerebral ischemia/reperfusion injury in rats[J]. Experimental & Therapeutic Medicine, 2016, 11(3): 1045-1050.

[2] Peter L Kolominsky-Rabas, Silke Wiedmann, Michael Weingartner, et al. Time trends in incidence of pathological and etiological stroke subtypes during 16 years: the erlangen stroke project[J]. Neuroepidemiology, 2015, 44(1): 24-29.

[3] Min Wang, Li Yu-jiao, Yi Ding, et al. Silibinin prevents autophagic cell death upon oxidative stress in cortical neurons and cerebral ischemia-reperfusion injury[J]. Molecular Neurobiology, 2016, 53(2): 932-943.

[4] Thomas Westermaier, Christian Stetter, Ekkehard Kunze, et al. Magnesium treatment for neuroprotection in ischemic diseases of the brain[J]. Experimental & Translational Stroke Medicine, 2013, 5(1): 1-10.

[5] Ritu Saxena, Stephanie Lewis, Eivind Berge, et al. Risk of early death and recurrent stroke and effect of heparin in 3169 patients with acute ischemic stroke and trial fibrillation in the international Stroke Trial[J]. Stroke, 2001, 32(10): 2333-2337.

[6] Chen Min, Lu Ting-jia, Chen Xiao-jing, et al. Differential roles of NMDA receptor subtypes in ischemic neuronal cell death and ischemic tolerance[J]. Stroke, 2008, 39(11): 3042-3048.

[7] Gao Hai-jun, Liu Peng-fei, Li Pei-wen, et al. Ligustrazine monomer against cerebral ischemia/reperfusion injury[J]. Neural Regeneration Research, 2015, 10(5): 832-840.

[8] 王钊, 黄雨蒙. 氧化应激与脑缺血-再灌注损伤[J]. 临床与病理杂志, 2012, 3(4): 343-346.

[9] Elizabeth D Hood, Michael Chorny, Colin F Greineder, et al. Endothelial targeting of nanocarriers loaded with antioxidant enzymes for protection against vascular oxidative stress and inflammation[J]. Biomaterials, 2014, 35(11): 3708-3715.

[10] Arnadi Ramachandrayya Shivashankara, Jasmi Joy, Venkatesh Sunitha, et al. Effect of cell phone use on salivary total protein, enzymes and oxidative stress markers in young adults: A pilot study[J]. J Clinical & Diagnostic Research Jcdr, 2015, 9(2): 19-22.

[11] Hyakkoku K, Hamanaka J, Tsuruma K, et al. Toll-like recrptor 4 (TLR4), but not TLR3 or TLR9 knock-out mice have neuroprotective effects against focal focal cerebral ischemia[J]. Neuroscience, 2010, 17(1): 258–267.

[12] Cao Can-xiang, Yang Qing-wu, Lv Feng-lin, et al. Reduced focal cerebral ischemia/reperfusion injury in toll-like receptor 4 deficient mice[J]. Biochem Bioph Res Co, 2007, 353(2): 509–514.

[13] Jaroslaw Aronowski, Zhao Xiu-rong. Molecular pathophysiology of cerebral hemorrhage: secondary brain injury[J]. Stroke, 2011, 42(6): 1781-1786.

[14] 郭云良, 沈卫, 杜芳, 等. 胡黄连苷Ⅱ对大鼠脑缺血再灌注损伤后TLR-4及NFκB表达的影响[J]. 中国中西医结合杂志, 2011, 31(1): 58-61.

[15] 黎晓, 刘瑞珍, 林或夫, 等. 大豆苷元通过抑制炎症反应对大鼠脑缺血再灌注损伤保护作用的研究[J]. 时珍国医国药, 2014, (1): 6-8.

[16] 邓昌, 欧阳波, 陶然, 等. 虫草素对小鼠脑缺血再灌注损伤的神经保护作用及炎症调节[J]. 中国老年学杂志, 2014, 34(3): 687-690.

[17] 郭浩, 李磊, 侯金才, 等. 中药促治疗性血管新生防治缺血性心脑血管疾病的研究进展[J]. 中国中药杂志, 2015, 40(1): 24-28.

[18] Fang An, Xin-xin Cao, Hai-qi Qu, et al. Attenuation of oxidative stress of erythrocytes by the plant-derived flavonoids vitexin and apigenin[J]. Die Pharmazie, 2015, 70(11): 724-732.

[19] Fang An, Shu-lin Wang, Dan-hua Yuan, et al. Attenuation of oxidate stress of erythrocytes by plant-derived flavonoids-orientin and luteolin[J]. Evidence-Based Complementary and Alternative Medicine, 2016, 2016(1): 1-8.

[20] Fang An, Shu-hua Wang, Qing-qing Tian, et al. Effects of orientin and vitexin from Trollius chinensis on the growth and apoptosis of esophageal cancer EC-109 cells[J]. Oncology Letters, 2015, 10(4): 2627.

[21] Longa, E.Z, Zea Longa EL, Carlson S, et al. Cummins R, Weinstein PR Reversible middle cerebral artery occlusion without craniectomy in rats[J]. Stroke, 1989. 20(1): 84-91.

[22] 孟凛冽, 李峰, 伞勇智, 等. 帕金森病氧化应激机制及抗氧化药物治疗进展[J]. 现代生物医学进展, 2015, 15(2): 380-383.

[23] Yang W J, Hong Z, Tan S M, et al. Research progress of the effect and mechanism of oxidative stress on vasoactive substances[J]. J Pharmaceutical Research, 2015, 12(1): 1-10.

[24] Rodrigo J, Fernández A P, Serrano J, et al. The role of free radicals in cerebral hypoxia and ischemia[J]. Free Radical Biology & Medicine, 2005, 39(1): 26-50.

[25] Marian Valko, Klaudia Jomova, Christopher J Rhodes, et al. Redox- and non-redox-metal-induced formation of free radicals and their role in human disease[J]. Archives of Toxicology, 2016, 90(1): 1-37.

[26] 刘瑞. ROS介导的以Nrf2为核心的抗氧化防御体系对肺纤维化的调控机制研究[D]. 西安: 第四军医大学, 2008.

[27] 王姿颖，张岫美，魏欣冰等. 异黄酮类化合物N-2035对大鼠局灶性脑缺血再灌注脑组织损伤的保护作用（抗氧化活性）[J]. 山东大学学报: 医学版, 2003, 41(1): 36-38.

[28] Papadopoulos M C, Saadoun S, Binder D K, et al. Molecular mechanisms of brain tumor edema[J]. Neuroscience, 2004, 129(4): 1009-1018.

[29] Murphy G T, Mackenzie A, Guy-Walker J, et al. Regulation and function of aqp4 in the central nervous system[J]. Pediatrics, 2015, 51(12): 1-13.

[30] Joseph Cannova, Peter Breslin Peter S J, Zhang Ji-wang. Toll-like receptor signaling in hematopoietic homeostasis and the pathogenesis of hematologic diseases[J]. Frontiers of Medicine, 2015, 9(3): 288-303.

[31] Li Shuang-shuang, Gao Xiang-li, Wu Xiao-xin, et al. Parthenolide inhibits LPS-induced inflammatory cytokines through the toll-like receptor 4 signal pathway in THP-1 cells[J]. Acta Biochimica Et Biophysica Sinica, 2015, 47(5): 368-375.

[32] Nir Erdinest, Gal Aviel, Eli Moallem, et al. Expression and activation of toll-like receptor 3 and toll-like receptor 4 on human corneal epithelial and conjunctival fibroblasts[J]. J Inflammation, 2014, 11(1): 1-10.

[33] Neng Yang, Pan Wang, Wen-Juan Wang, et al. Inhibition of cathepsin L sensitizes human glioma cells to ionizing radiation in vitro through NF-κB signaling pathway[J]. Acta Pharmacologica Sinica, 2015, 36(3): 400-410.

[34] Chulwon Kim, Somi K Cho, Ki-Dong Kim, et al. β-Caryophyllene oxide potentiates TNFα-induced apoptosis and inhibits invasion through down-modulation of NF-κB-regulated gene products[J]. Apoptosis, 2013, 19(4): 708-718.

[35] Orla Watters, John J O’Connor. A role for tumor necrosis factor-α in ischemia and ischemic preconditioning[J]. Journal of Neuroinflammation, 2011. 8(1): 1-8.

[36] 刘晖, 张嘉伟, 林宇, 等. 银杏内酯B对老龄大鼠局灶性脑缺血-再灌注损伤炎症反应的作用[J]. 中国老年学杂志, 2013, 33(13): 3139-3140.

[37] 梅志刚, 王明智, 刘晓洁, 等. 葛根素对大鼠脑缺血再灌注损伤α7nAChR、NF-кBp65及STAT3 mRNA表达的影响[J]. 中华中医药杂志, 2013, (1): 113-117.