JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2016, Vol. 54 ›› Issue (4): 25-31.doi: 10.6040/j.issn.1671-7554.0.2015.1079

Previous Articles     Next Articles

Neuroprotective effect of dl-3n-butylphthalide on focal cerebral ischemia reperfusion injury in rats

ZHAO Xiuqin1, DENG Chunying1, LI Shiying1, ZHANG Jinxia1, HE Yonggui1, YU Hong2, LIU Bin1   

  1. 1. Department of Neurology;
    2.Department of pharmacology, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan 063000, Heibei, China
  • Received:2015-11-06 Online:2016-04-10 Published:2016-04-10

PDF (PC)

432

Abstract: Objective To explore the neuroprotective effect of dl-3n-butylphthalide(NBP)on focal cerebral ischemia reperfusion injury in rats and to investigate the possible mechanism. Methods A total of 75 male Sprague-Dawley(SD)rats were randomly divided into Sham operation group(Sham group), ischemia/reperfusion injury group(IR group), high-dose NBP post-treatment group(high-dose group), medium-dose NBP post-treatment group(medium-dose group)and low-dose NBP post-treatment group(low-dose group), with 15 rats in each group. Focal cerebral ischemia reperfusion model was established with middle cerebral artery occlusion(MCAO)by modified cerebral artery ligation. At 24 h after 2 hours reperfusion, neurological deficits and the infarct volume were measured. TdT-mediated dUTP nick-end labeling(TUNEL)was used to observe the expression of neuronal apoptosis. Immunohistochemistry was used to observe silent mating type information regulation 2 homolog 1(SIRT1)and peroxisome proliferator-activated receptor-γ coactivator-1α(PGC-1α)positive cells. Quantitative Real-time PCR was used to observe the expression of SIRT1 and PGC-1α mRNA. Results The rats in Sham group showed no obvious neurological deficit symptoms and no 山 东 大 学 学 报 (医 学 版)54卷4期 -赵秀芹,等.丁苯酞注射液对大鼠局灶性脑缺血再灌注损伤的神经保护作用 \=-infarct size. Compared with Sham group, the number of apoptotic cells increased in IR group and three dosage levels of NBP post-treatment group(P<0.05), so were the number of SIRT1 and PGC-1α positive cells and the expression of SIRT1 and PGC-1α mRNA(P<0.05). Compared with IR group, the neurological deficit scores decreased in each three dosage level of NBP post-treatment group(P<0.05), so were the infarct size and the number of apoptotic cells(P<0.05), while the number of SIRT1 and PGC-1α positive cells and the expression of SIRT1 and PGC-1α mRNA in NBP post-treatment group were increased(P<0.05). Compared with medium- or low- dose group, the high-dose group had lowest neurological deficit scores, infarct size and the number of apoptotic cells, but highest number of SIRT1 and PGC-1α positive cells and the expression of SIRT1 and PGC-1α mRNA, with significant difference(P<0.05). Conclusion NBP injection can relieve the brain damage induced by focal cerebral ischemia reperfusion in rats, which potentially related to the up-regulation of SIRT1 and PGC-1α expression.

Key words: Butylphthalide, Focal cerebral ischemia reperfuson, Silent mating type information regulation 2 homolog 1, Peroxisome proliferator-activated receptor-γ coactivator-1α, Neuroprotective effect

CLC Number: 

  • R743
[1] Chen L,Wang L,Zhang X,et al.The protection by octreotide against experimental ischemic stroke: up-regulated transcription factor Nrf2,Ho-1 and down-regulated NF-kB experssion[J]. Brain Res, 2012, 1475:80-87. doi:10.1016/j.brainres.2012.07.052.
[2] 陆征宇, 董强. 脑缺血后神经血管保护机制和损伤机制研究进展[J/OL].中华脑血管病杂志,2013,7(3):34-40. LU Zhengyu, DONG Qiang.Progress of neurovoscular protective and mechanism research after cerebral ischemia[J/OL].Chin J Cerebrovasc Dis, 2013, 7(3):34-40.
[3] 王伟, 李富强, 邓小影, 等. 丁苯酞预处理对缺血再灌注损伤后大鼠海马神经元的保护作用[J]. 临床神经病学杂志, 2015, 28(1):42-45. WANG Wei, LI Fuqiang, DENG Xiaoying, et al. Protective effects of 3-n-butylphthalide pretreatment on hippocampal neurous of rats after cerebral ischemia reperfusion injury[J]. J Clin Neurol, 2015, 18(1):42-45.
[4] Zhang T, Jia W, Sun X, et al. 3-n-Butylphthalide(NBP)reduces apoptosis and enhances vascular endothelial growth factor(VEGF)up-regulation in diabetic rats[J]. Neurol Res, 2010, 32(4):390-396.
[5] Zhao Q, Zhang C, Wang X, et al.(S)-ZJM-289, a nitric oxide-releasing derivative of 3-n-butylphthalide, protects against ischemic neuronal injury by attenuating mitochondrial dysfunction and associated cell death[J]. Neurochem Int, 2012, 60(2):134-144.
[6] Longa EZ, Weistein PR, Calson S, et al. Reversible middle cerebral artery occlousion without craniectomy in rats[J].Stroke, 1989, 20(1):84-91.
[7] 孙国兵, 许康, 赵薛旭, 等. 丁苯肽软胶囊对脑缺血大鼠神经保护作用研究[J/OL].中华临床医师杂志, 2013, 7(10):4391-4394. SUN Guobing, XU Kang, ZHAO Xuexu, et al. Neuroprotective effect of butylphthalide in cerebral ischemic rats[J/OL]. Chin J Clinicians, 2013, 7(10):4391-4394.
[8] 魏微, 张微微, 王娟, 等. 丁苯肽对慢性低灌注大鼠血-脑脊液屏障保护作用的研究[J]. 神经损伤与功能重建, 2010, 5(5):335-337. WEI Wei, ZHANG Weiei, WANG Juan, et al. A study on protective role of butylphthalide on blood-brian barrier in rats with chronic hypoperfusion[J]. Neural Injury and Functional Reconstruction, 2010, 5(5):335-337.
[9] 吴玉杰, 梁玉鑫, 徐燕玲. 奥扎格雷联合丁苯肽对大鼠脑缺血再灌注损伤保护作用机制的研究[J]. 安徽医学, 2013, 34(8):1066-1067. WU Yujie, LIANG Yuxin, XU Yanling. Study on protective effect of ozagrel hydrochloride combined with butylphthalide in treatment of cerebral ischemia-reperfusion injury in rats [J]. Anhui Med J, 2013, 34(8):1066-1067.
[10] 宁文婧, 杜业亮, 孙乐津. 丁苯酞对脑缺血大鼠AQP9mRNA表达的影响[J].中国实用神经疾病杂志, 2014, 17(4):52-54. NING Wenjing, DU Yeliang, SUN Lejin. Effect of butylphthalide on expression of AQP9mRNA in rats with cerebral ischemia-reperfusion injury[J]. Chin J Pract Nerv Dise, 2014, 17(4):52-54.
[11] 李秋霞, 陈淅泠, 王欣东, 等. 丁苯酞注射液对血管性痴呆大鼠海马区生长相关蛋白-43及突触素P38表达的影响[J].实用医学杂志, 2012, 28(7):1067-1069. LI Qiuxia, CHEN Xiling, WANG Xindong, et al. Effect of butylphthalide on growth associated protein-43 and expression of synaptophysin 38 in rats with vascular dementia[J]. J Pract Med, 2012, 28(7):1067-1069.
[12] 郑献召, 张三军, 石莉, 等. 丁苯酞治疗大鼠脑缺血再灌注损伤作用机制的研究[J]. 中国实用神经病学杂志, 2009, 12(23):59-61. ZHENG Xianzhao, ZHANG Sanjun, SHI Li, et al. Study on neuroprotective effect of butylphthalide in rats with cerebral ischemia-reperfusion injury[J]. Chin J Pract Nerv Dise, 2009, 12(23):59-61.
[13] Sugino T, Maruyama M, Tanno M, et al.Protein deacetylase SIRT1 in the cytoplasm promotes nerve growth factor-induced neurite outgrowth in PC12 cells[J].FEBS Lett, 2010, 584(13):2821-2826.
[14] 曲柳, 仇丽鸿. SIRT1抑制炎症反应的研究进展[J].中国实用口腔科杂志,2013,6(9):566-570. QU Liu, QIU Lihong. Reseach progress of SIRT1 in suppressing inflammatory response[J]. Chin J Pract Stomat, 2013, 6(9):566-570.
[15] Donmez G, Wang D, Cohen DE, et al. SIRT1 suppresses beta-amyloid production by activating the alpha-secretase gene ADAM10[J]. Cell, 2010, 142(2):320-332.
[16] Morris KC, Lin HW, Thompson JW, et al. Pathways for ischemic cytoprotection:role of sirtuins in caloric restriction, resveratrol, and ischemic preconditioning[J]. J Cereb Blood Flow Metab, 2011, 31(4):1003-1019.
[17] Yan WJ, Fang ZP, Yang QZ, et al. SirT1 mediates hyperbaric oxygen preconditioning-induced ischemic tolerance in rat brain[J]. J Cereb Blood Flow Metab, 2013, 33(3):396-406.
[18] Scarpulla RC. Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network[J]. Biochim Biophys Acta, 2010, 1813(7):1269-1278.
[19] Chen SD, Lin TK, Yang DI, et al. Protective effects of peroxisome proliferator-activated receptors gamma coactivator-1alpha against neuronal cell death in the hippocampal CA1 subfield after transient global ischemia[J]. Neurosci Res, 2010, 88(3):605-613.
[20] Shiota M,Yokomizo A, Tada Y, et al.Peroxisome proliferator- activated receptor gamma coactivator-1alpha interacts with the androgen receptor(AR)and promotes prostate cancer cell growth by activating the AR[J]. Mol Endocrinol, 2010, 24(1):114-127.
[21] St-Pierre J, Drori S, Uldry M, et al. Suppression of reaetive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators[J]. Cell, 2006, 127(2):397-408.
[22] Chen SD, Lin TK, Yang DI, et al. Protective effects of peroxisome proliferator-activated receptors γ coactivator-1α against neuronal cell death in the hippocampal CA1 subfield after transient global ischemia[J]. J Neurosci Res, 2010, 88(3):605-613.
[23] Canto C, Auwerx J. PGC-l alPha, SIRTI and AMPK, an energy sensing network that eonirols energy expenditure[J].Curr Opin Lipidol, 2009, 20(2):98-105.
[24] Wareski P, Vaarmann A, Choubey V, et al. PGC-l{alPha}and PGC-l{beta} regulate mitoehondrial density in neurons[J].J Biol Chem, 2009, 284(32):21379-21385.
[1] YAN Jinxiang, MENG Lei, DONG Yanan, ZHANG Aijun, YUE Hongsheng, LI Bo, ZHONG Liangjun, BAI Aiguo. Application of Solitaire FR stent in the optimized treatment of acute cerebral artery occlusion [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(7): 49-54.
[2] LI Jiqing, ZHAO Huanzong, SONG Binghong, ZHANG Lichun, LI Xiangyi, CHEN Yafei, WANG Ping, XUE Fuzhong. Risk prediction model of cardiovascular disease based on health management cohort [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(6): 56-60.
[3] LI Min, WANG Chunxia, XIA Bing, ZHU Qian, SUN Yuanying, WANG Shukang, XUE Fuzhong, JIA Hongying. A stroke prediction model for the health management population [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(6): 93-97.
[4] WANG Weijun, ZHOU Ningquan, WANG Chao. Treatment of 68 cases of moderate volume of hypertensive intracerebral hemorrhage with free hand technique of minimally invasive puncture of the soft channel under CT orientation [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(5): 61-65.
[5] . [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(4): 114-116.
[6] QU Lixin, SHI Xinghua, DU Yifeng. Relationship between circulating platelets microparticles and endothelial microparticls and prognosis in patients with acute ischemic stroke [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(12): 32-36.
[7] . [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(11): 90-92.
[8] DONG Fang, DU Yifeng. Correlation among cognitive impairment and high homocysteinemia as well as the number and volume of infarct in patients with lacunar cerebral infarction [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(10): 46-49.
[9] MI Te, QU Chuanqiang, WANG Xiang, YIN Ling, XUE Yuan, DU Yifeng. Correlation between serum amyloid A and cognitive function of patients with acute cerebral infarction [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(10): 40-45.
[10] LIU Jie, LIU Jinzhi, LIN Yan, HUANG Zhan, WANG Aihua. Effects of thrombolytic therapy with broadened therapeutic window on the free radical activity and the expression of Caspase-3 in a rat model of acute cerebral infarction [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(4): 26-30.
[11] YU Lei, LI Zhen. Expression of interleukin-33 and its function in the serum of patients with cerebrovascular disease [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(4): 75-79.
[12] FAN Shaohua, ZHANG Yichao, YUAN Xiaodong, BI Jingwen, ZHANG Yichen, LI Yun. Expressions of MiR210 and stat3 following global ischemia in rats and the potential relationship among MiR210, stat3 and HIF-1α [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(3): 1-5.
[13] . [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(S2): 59-60.
[14] FU Qingyuan, DAI Guiqiang, ZHANG Song, AN Hongchun, LIANG Shimin. Effect of panax quinquefolium saponin from stems and leaves on endothelin-1, vascular endothelial growth factor and infarct area in rats [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(9): 30-33.
[15] LIN Yan1, LIU Jinzhi1, LIU Jie1, YANG Qianqian2, SI Zhihua1, XU Shan1, WANG Aihua1. Effects of thrombolytic therapy with broadened therapeutic window on infarct volume, microvessel density and adherence factors in acute cerebral infarction [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(5): 20-24.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd