柿叶黄酮类化合物对APP/PS1转基因小鼠脑组织突触的保护作用

doi:10.6040/j.issn.1671-7554.0.2015.705

摘要/Abstract

摘要： 目的探讨柿叶黄酮类提取物(FLDK)对APP/PS1小鼠认知水平、突触结构及突触相关蛋白表达的影响。方法 20只4月龄APP/PS1小鼠,随机分为阿尔茨海默病(AD)模型组(AD组)及治疗组(AD+FLDK组),每组10只;10只4月龄C57BL/6小鼠为正常对照组(NC组)。AD+FLDK组给予FLDK 80 mg/(kg·d)灌胃干预60 d,AD组与NC组同样方法给予等量生理盐水60 d。分别采用Morris水迷宫测试小鼠逃避潜伏期(EL)及穿越平台次数,电镜观察突触超微结构,并用免疫组织化学方法检测皮层及海马区突触素(SYP)和大脑发育调节蛋白(drebrin)的含量。结果与NC组相比,AD组小鼠EL明显延长,穿越平台次数显著减少,突触结构模糊,SYP及drebrin表达明显减少。与AD组相比,AD+FLDK组EL减少,穿越平台次数明显增多,突触结构更完整且SYP、drebrin表达显著增加。结论 FLDK可显著改善APP/PS1小鼠学习记忆水平,增强突触结构完整性,提高突触相关蛋白含量,具有认知及突触保护作用。

关键词: 柿, 黄酮, APP/PS1, 认知, 突触

Abstract: Objective To investigate the effect of flavonoids extracted from the leaves of Diospyros kaki(FLDK)on cognition levels, synapse structure and the expression of synapse-related proteins in APP/PS1 transgenic mouse. Methods Twenty APP/PS1 mice of four-month old were randomly divided into Alzheimers disease(AD)model group(AD group)and treatment group(AD+FLDK group), ten in each group; ten C57BL/6 mice of four-month old were regarded as normal control group(NC group). AD+FLDK group was treated intragastrically with 80 mg/(kg·d)FLDK, while AD and NC groups were fed intragastrically with the same volume of normal saline. Morris water maze was used to test the escape latency(EL)and number of crossing, transmission electron microscope was used to observe the ultrastructure of synapse, and immunohistochemistry was used to detect the expression levels of synaptophysin and drebrin. Results Compared with NC group, the EL was prolonged, crossing numbers decreased, the synapse ultrastructure was damaged and synapse-related protein levels decreased in AD group. Compared with AD group, EL decreased and crossing number increased obviously, synapse ultrastructure was clearer and synapse-related protein levels increased in AD+FLDK group. Conclusion FLDK can improve cognitive decline in APP/PS1 transgenic mouse, protect the integrity of synapse, and increase the synapse-related protein levels, thus can enhance cognition levels and protect synapse.

Key words: Flavonoids, Cognition, Diospyros kaki, APP/PS1, Synapse

中图分类号:

R741.05

尚玉莹,马莹娟,吴小凡,侯训尧,罗鼎真,陈健,洪燕,申超,刘雪平. 柿叶黄酮类化合物对APP/PS1转基因小鼠脑组织突触的保护作用[J]. 山东大学学报（医学版）, 2016, 54(2): 33-37.

SHANG Yuying, MA Yingjuan, WU Xiaofan, HOU Xunyao, LUO Dingzhen, CHEN Jian, HONG Yan, SHEN Chao, LIU Xueping. Synapse-protective effect of flavonoids extracted from the leaves of Diospyros kaki in APP/PS1 transgenic mice[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(2): 33-37.

参考文献

[1] Lin N, Pan XD, Chen AQ, et al. Tripchlorolide improves age-associated cognitive deficits by reversing hippocampal synaptic plasticity impairment and NMDA receptor dysfunction in SAMP8 mice[J]. Behav Brain Res, 2013, 258(2014):8-18.
[2] Oliveira DR, Sanada PF, Saragossa FA, et al. Neuromodulatory property of standardized extract Ginkgo biloba L.(EGb 761)on memory:behavioral and molecular evidence[J]. Brain Res, 2009, 1269:68-89.
[3] Walker JM, Klakotskaia D, Ajit D, et al. Beneficial effects of dietary EGCG and voluntary exercise on behavior in an Alzheimers disease mouse model.[J]. J Alzheimers Dis, 2015, 44(2):561-572.
[4] Rendeiro C, Vauzour D, Kean RJ, et al. Blueberry supplementation induces spatial memory improvements and region-specific regulation of hippocampal BDNF mRNA expression in young rats[J]. Psychopharmacology(Berl), 2012, 223(3):319-330.
[5] Li H, Wu X, Wu Q, et al. Green tea polyphenols protect against okadaic acid-induced acute learning and memory impairments in rats[J]. Nutrition, 2014, 30(3):337-342.
[6] Williams CM, El Mohsen MA, Vauzour D, et al. Blueberry-induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor(BDNF)levels[J]. Free Radic Biol Med, 2008, 45(3):295-305.
[7] Bei W, Peng W, Zang L, et al. Neuroprotective effects of a standardized extract of Diospyros kaki leaves on MCAO transient focal cerebral ischemic rats and cultured neurons injured by glutamate or hypoxia[J]. Planta Med, 2007, 73(7):636-643.
[8] Gandhi S, Abramov AY. Mechanism of oxidative stress in neurodegeneration[J]. Oxid Med Cell Longev, 2012:428010.
[9] Rao JS, Kellom M, Kim HW, et al. Neuroinflammation and synaptic loss[J]. Neurochem Res, 2012, 37(5):903-910.
[10] Selkoe DJ. Alzheimers disease is a synaptic failure[J]. Science, 2002, 298(5594):789-791.
[11] Trinchese F, Liu S, Battaglia F, et al. Progressive age-related development of Alzheimer-like pathology in APP/PS1 mice[J]. Ann Neurol, 2004, 55(6):801-814.
[12] Yu YF, Zhai F, Dai CF, et al. The relationship between age-related hearing loss and synaptic changes in the hippocampus of C57BL/6J mice[J]. Exp Gerontol, 2011, 46(9):716-722.
[13] Lin YC, Yeckel MF, Koleske AJ. Abl2/Arg controls dendritic spine and dendrite arbor stability via distinct cytoskeletal control pathways[J]. J Neurosci, 2013, 33(5):1846-1857.
[14] Aoki C, Sekino Y, Hanamura K, et al. Drebrin A is a postsynaptic protein that localizes in vivo to the submembranous surface of dendritic sites forming excitatory synapses[J]. J Comp Neurol, 2005, 483(4):383-402.
[15] Merriam EB, Lumbard DC, Viesselmann C, et al. Dynamic microtubules promote synaptic NMDA receptor-dependent spine enlargement[J]. PLoS One, 2011, 6(11):e27688. doi:10.1371/journal.pone.0027688.
[16] 马丽娜,王蓉. 大脑发育调节脑蛋白对神经元树突棘及突触可塑性的影响[J]. 中华老年心脑血管病杂志, 2013, 15(10):1109-1111.
[17] Shim KS, Lubec G. Drebrin, a dendritic spine protein, is manifold decreased in brains of patients with Alzheimers disease and Down syndrome[J]. Neurosci Lett, 2002, 324(3):209-212.
[18] Lee D, Aoki C. Presenilin conditional double knockout mice exhibit decreases in drebrin a at hippocampal CA1 synapses[J]. Synapse, 2012, 66(10):870-879.
[19] Volk LJ, Bachman JL, Johnson R, et al. PKM-zeta is not required for hippocampal synaptic plasticity, learning and memory[J]. Nature, 2013, 493(7432):420-423.
[20] Prakash D, Gopinath K, Sudhandiran G. Fisetin enhances behavioral performances and attenuates reactive gliosis and inflammation during aluminum chloride-induced neurotoxicity[J]. Neuromolecular Med, 2013, 15(1):192-208.
[21] Zhao L, Wang JL, Wang YR, et al. Apigenin attenuates copper-mediated beta-amyloid neurotoxicity through antioxidation, mitochondrion protection and MAPK signal inactivation in an AD cell model[J]. Brain Res, 2013, 1492:33- 45.

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