白藜芦醇对大鼠脑缺血再灌注损伤后突触素表达的影响

摘要/Abstract

摘要： [摘要] 目的研究白藜芦醇对大鼠脑缺血再灌注损伤后突触素表达的影响。方法 60只SD雄性大鼠随机分成假手术组(Sham)、缺血对照组(Con)和白藜芦醇组(Res)，每组20只。缺血3 h后腹腔注射白藜芦醇或无水乙醇，连用7 d。脑缺血24 h时，TTC法测量脑梗死体积，干湿称重法检测脑含水量。缺血24 h、7 d、14 d分别行Bederson神经功能缺损评分、免疫组化法及Western blot检测突触素蛋白的表达。结果 TTC染色显示对照组和白藜芦醇组梗死体积较假手术组高（P < 0. 05），而白藜芦醇组较对照组显著减小(P < 0. 05)。脑含水量检测显示对照组和白藜芦醇组较假手术组明显增高（P < 0. 05），但白藜芦醇组较对照组显著降低（P< 0. 05）。神经功能缺损评分显示24 h、7 d、14 d对照组和白藜芦醇组显著高于假手术组（P < 0. 05），但白藜芦醇组较对照组显著降低（P < 0. 05）。免疫组化显示对照组24h时脑缺血皮质突触素阳性表达减少，7 d 、14 d时逐渐增加，但均较假手术组显著减少。白藜芦醇组各时间点均较对照组明显增加，14 d增加更明显。WB显示对照组24 h、7 d、14 d脑缺血区皮质突触素蛋白表达较假手术组显著降低（P < 0. 05），但7 d 、14 d时逐渐增加；白藜芦醇组各时间点较缺血对照组显著增强（P < 0. 05），14 d时增加更显著。结论白藜芦醇治疗可增强脑缺血大鼠突触素的表达，改善神经功能。

关键词: 白藜芦醇, 脑缺血再灌注, 突触素, 表达, 大鼠

Abstract: [Abstract] Objective To examinate the effect of resveratrol on expression of synaptophysin after cerebral ischemia/reperfusion injury in rats. Methods 60 male Sprague-Dawley rats were divided into sham, ischemic control and resveratrol group. Each group is 20 rats. The rats were treated with resveratrol or ethyl alcohol by intraperitoneally for 7 consecutive days after 3 h for MCAO. At 24 h after MCAO/R, TTC assay examinated cerebral infarction volume and dry and wet weight method tested moisture content in brain tissue. At 24 h, 7 d and 14 d after MCAO/R, we examinated the neurological function score with Bederson score and the protein expression of synaptophysin in ischemic cortex with immunohistochemistry and Western blot. Results The infarction volumes in the control and resveratrol group were significantly higher than in the sham group (P < 0. 05), and it was significantly lower in the resveratrol group than in the control group (P < 0. 05).Brain water contents in the control and resveratrol group were significantly higher than in the sham group (P < 0. 05), and it was significantly lower in the resveratrol group than in the control group (P < 0. 05). The neurological function score in the control and resveratrol group were significantly higher than in the sham group at 24 h, 7 d and 14 d (P < 0. 05), and it was significantly lower in the resveratrol group than in the control group (P < 0. 05). Immunohistochemistry display that the positive expression of synaptophysin in ischemic cortex in the control group were reduced at 24 h, and increased gradually at 7 d and 14 d, but were significantly lower than in the sham group. After resveratrol treatment, it was significantly higher than in the control group at each point time, and was highest at 14 d. Western blot assay showed that the protein expression of synaptophysin in the control group was significantly lower than in the sham group at 24 h, 7 d and 14 d after MCAO/R (P < 0. 05), but gradually increased at 7 d and 14 d. After resveratrol treatment, it was significantly enhanced than in the control group at each point time (P < 0. 05), and was strongest at 14 d. Conclusion Resveratrol treatment can enhance the expression of synaptophysin and improve neurological function.

Key words: Resveratrol, Cerebral ischemia/reperfusion , Synaptophysin , Expression , Rat

余萍萍王莉唐凡人周露玲曾立杨琴. 白藜芦醇对大鼠脑缺血再灌注损伤后突触素表达的影响[J]. , 2016, 47(1): 12-17.

参考文献

[1]Rodgers H.Strok[J].HandbClin Neurol, 2013, 110(1):427-433 [2]Ruan YW, Han XJ, Shi ZS, et al.Remodeling of synapses in the CA1 area of the hippocampus after transient global ischemia[J].Neuroscience, 2012, 218(1):268-277 [3]Costain WJ, Rasquinha I, Sandhu JK, et al.Cerebral ischemia causes dysregulation of synaptic adhesion in mouse synaptosomes[J].Cereb Blood Flow Metab, 2008, 28(1):99-110 [4]Neumann JT, Cohan CH, Dave KR, Wright CB, Perez-Pinzon MA.Global cerebral ischemia: synaptic and cognitive dysfunction[J].Curr Drug Targets, 2013, 14(1):20-35 [5] Brisdelli F, D'Andrea G, Bozzi A.Resveratrol: a natural polyphenol with multiple chemopreventiveproperties[J].Curr Drug Metab, 2009, 10(6):530-546 [6]Pangeni R, Sahni JK, Ali J, et al.. Resveratrol: review on therapeutic potential and recent advances in drug delivery[J].Expert Opin Drug Deliv, 2014, 11(8):1285-1298 [7] Ren J, Fan C, Chen N.et al.Resveratrol pretreatment attenuates cerebral ischemic injury by upregulating expression of transcription factor Nrf2 and HO-1 in rats[J]. . 2011. 36(12): 2352-62.[J].Neurochem Res, , :- [8] Cheng W, Yu P, Wang L .et al. Sonic hedgehog signaling mediates resveratrol to increase proliferation of neural stem cells after oxygen-glucose deprivation/reoxygenation injury in vitro[J].Cell PhysiolBiochem 2015;35:2019-2032. [9]任俊伟, 杨琴。白藜芦醇对大鼠脑缺血再灌注氧化应激损伤的影响[J].中国生物制品学杂志. 2011. (03): 292-296. [10]任俊伟, 杨琴, 陈娜等白藜芦醇对脑缺血再灌注后细胞凋亡及Caspase-3表达的影响[J].中成药. 2011. (04): 570-573. [11]沈长波，黄家贵，张黎黎等.白藜芦醇在缺血缺氧再灌注损伤不同时间窗皮质神经元氧化应激的影响[J].第二军医大学学报, 2013, 7月20日，34(7):708-713 [12]Longa EZ, Weinstein PR, Carlson S, et al.Reversible middle cerebral artery occlusion without craniectomy in rats[J]. Stroke. 1989. 20(1): 84-91. [13] Bederson JB，Pitts LH，Tsuji M，et al． Rat middle cerebral artery occlusion：evaluation of the mordel and development of neurologic examination[J]．Stroke， 1986，17：472—476. [14] 张黎黎，黄家贵，沈长波等。白藜芦醇预处理对缺糖缺氧再灌注损伤大鼠原代皮质神经元的保护作用及机制[J].中成药。2014,5月20日，36（5）：898-903. [15]. 成薇，沈长波，王莉等。白藜芦醇预处理对氧糖剥夺/再复氧损伤大鼠皮质神经干细胞增殖的影响[J]。中国药理学通报。2015,1月20日，31（1）：113-118。 [16] Li, Z.,Pang,L.,Fang,F.,Zhang,G.,Zhang,J.,Xie,M.,andWang,L. Resveratrol attenuates brain damage in a rat model offocal cerebral ischemia via up-regulation of hippocampal Bcl-2. BrainRes. 2012; 1450,116 ?124. [17] Dong W, Li N, Gao D, et al.Resveratrolattenuates ischemic brain damage in thedelayedphase afterstrokeand induces messenger RNA and protein express for angiogenic factors[J]. J Vasc Surg.2008 Sep;48(3):709-14. [18]Clark D, Tuor UI, Thompson R, et al.Protection against recurrentstrokewithresveratrol: endothelial protection[J].PLoS One.2012;7(10):e47792. [19]Martinez G, Di GC, Carnazza ML, et al.MAP2,synaptophysin immunostaining in rat brain and behavioral modifications after cerebral postischemic reperfusion[J]. Dev Neurosci. 1997. 19(6): 457-64. [20]Murphy TH, Corbett D.Plasticity during stroke recovery: from synapse to behaviour[J]. Nat Rev Neurosci. 2009. 10(12): 861-72. [21]Valtorta F, Pennuto M, Bonanomi D, et al.Synaptophysin: leading actor or walk-on role in synaptic vesicle exocytosis[J]. Bioessays. 2004. 26(4): 445-53.