杨志友,马智慧,张永平,宋采,胡雪琼

• 1:广东海洋大学食品科技学院//广东省水产品加工与安全重点实验室//广东省海洋生物制品工程实验室//广东省海洋食品工程技术研究中心//水产品深加工广东普通高等学校重点实验室
• 2:大连工业大学海洋食品精深加工关键技术省部共建协同创新中心

摘要(Abstract)：

【目的】研究海带岩藻多糖(Fucoidan)对Aβ25-35(Amyloidβ)诱导原代皮层神经突起萎缩和神经元凋亡的抑制作用。【方法】以Aβ25-35诱导的人神经母细胞瘤细胞(SH-SY5Y)和原代小鼠皮层神经元损伤为模型,采用CCK8法测定细胞存活率,免疫细胞化学法测定岩藻多糖对神经突起再生和神经元的保护作用。【结果】CCK8结果表明,岩藻多糖在0.1～1 000μg/m L时对SH-SY5Y细胞无明显毒性作用(P> 0.05),在10～1 000μg/m L时可显著降低Aβ25-35诱导的SH-SY5Y细胞凋亡(P<0.05),且呈现浓度依赖性;对该结果在原代小鼠皮层神经元上进行验证,发现岩藻多糖在0.1～1.0 mg/m L浓度时显著降低Aβ25-35诱导的神经元凋亡(P <0.01),同时极显著抑制Aβ25-35造成的神经突起萎缩并促进突起再伸长(P <0.001)。【结论】海带岩藻多糖可显著抑制Aβ25-35诱导的神经突起萎缩和神经元凋亡,促进突起再生,提示其可作为阿尔茨海默病药物开发的先导化合物。

关键词(KeyWords)： 岩藻多糖;SH-SY5Y细胞;原代神经元;Aβ25-35;神经保护;突起萎缩;突起再生

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金（81803753）;; 广东省自然科学基金（2020A1515010779）

作者(Author): 杨志友,马智慧,张永平,宋采,胡雪琼

参考文献(References)：

• [1]TAN C C,YU J T,WANG H F,et al.Efficacy and safety of donepezil,galantamine,rivastigmine,and memantine for the treatment of Alzheimer's disease:a systematic review and meta-analysis[J].Journal of Alzheimer's Disease,2014,41(2):615-631.
• [2]TRICCO A C,SOOBIAH C,BERLINER S,et al.Efficacy and safety of cognitive enhancers for patients with mild cognitive impairment:a systematic review and meta-analysis[J].Canadian Medical Association journal,2013,185(16):1393-1401.
• [3]DICKSON T C,VICKERS J C.The morphological phenotype of beta-amyloid plaques and associated neuritic changes in Alzheimer’s disease[J].Neuroscience,2001,105(1):99-107.
• [4]TERRY R D,MASLIAH E,SALMON D P,et al.Physical basis of cognitive alterations in Alzheimer’s disease:Synapse loss is the major correlate of cognitive impairment[J].Annals of Neurology,1991,30(4):572-580.
• [5]SIEMERS E R,SUNDELL K L,CARLSON C,et al.Phase 3 solanezumab trials:Secondary outcomes in mild Alzheimer's disease patients[J].Alzheimer’s and Dementia,2016,12(2):110-120.
• [6]GAUTHIER S,FELDMAN H H,SCHNEIDER L S,et al.Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer's disease:a randomised,controlled,double-blind,parallel-arm,phase3 trial[J].Lancet,2016 388(10062):2873-2884.
• [7]ALOBUIA W M,XIA W,VOHRA B P S.Axon degeneration is key component of neuronal death in amyloid-βtoxicity[J].Neurochemistry International,2013,63(8):782-789.
• [8]PALOP J J,MUCKE L.Amyloid-βinduced neuronal dysfunction in Alzheimer’s disease:from synapses toward neural networks[J].Nature Neuroscience,2010,13(7):812-818.
• [9]李小蓉,张拴.海带中岩藻多糖的抗衰老活性及构效关系研究[J].食品工业科技,2015,36(15):117-121.
• [10]吴俊仙,董昀凡,袁涛,等.岩藻多糖对炎症性肠病的作用及其机制[J].南京医科大学学报(自然科学版),2019,39(9):1304-1313.
• [11]刘颖.低分子量海带岩藻多糖的制备及其抗肿瘤活性的研究[D].安徽：安徽农业大学,2012.
• [12]石磊,高欣,赵艳威,等.岩藻多糖对小鼠免疫功能的影响[J].食品研究与开发,2012,33(12):194-196.
• [13]王鸿,张甲生,严银春,等.褐藻岩藻多糖生物活性研究进展[J].浙江工业大学学报,2018,46(2):209-215.
• [14]GAO Y L,LI C M,YIN J G,et al.Fucoidan,a sulfated polysaccharide from brown algae,improves cognitive impairment induced by infusion of Aβpeptide in rats[J].Environmental Toxicology and Pharmacology,2012,33(2):304-311.
• [15]YANG Z Y,KUBOYAMA T,TOHDA C.A systematic strategy for discovering a therapeutic drug for Alzheimer’s disease and its target molecule[J].Frontiers in Pharmacology,2017,8:340.
• [16]安文强,黎文伟,谭北平,等.大规格凡纳滨对虾饲料中适宜钙磷添加水平[J].广东海洋大学学报,2018,38(4):8-19.
• [17]马智慧,杨志友.桃叶珊瑚苷对Aβ25-35诱导的突起萎缩和神经元凋亡的保护作用[J].中国药理学通报,2020,36(10):1391-1396.
• [18]SUBARAJA M,ANANTHA KRISHNAN D,EDWINHILLARY,et al.Fucoidan serves a neuroprotective effect in an Alzheimer's disease model[J].Frontiers in Bioscience (Elite Edition),2020,12:1-34.
• [19]BAI X,ZHANG E,HU B,et al.Study on absorption mechanism and tissue distribution of fucoidan[J].Molecules,2020,25(5):1087.
• [20]WANG X Y,SUN G Q,FENG T,et al.Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer's disease progression[J].Cell Research,2019,29(10):787-803.
• [21]黄娟,李华军.不同分子量fucoidan对免疫低下小鼠模型免疫功能及其肠道菌群调节作用的初步研究[C]//中国食品科学技术学会.第十五届益生菌与健康国际研讨会摘要集.南京：中国食品科学技术学会，2020:106-107.
• [22]WANG X,YI K,ZHAO Y.Fucoidan inhibits amyloid-β-induced toxicity in transgenic Caenorhabditis elegans by reducing the accumulation of amyloid-βand decreasing the production of reactive oxygen species[J].Food and Function,2018,9(1):552-560.
• [23]张甘霖,李萍,李玉洁,等.褐藻多糖硫酸酯通过溶酶体组织蛋白酶D调节过氧化氢诱导的PC12细胞凋亡[J].中国中药杂志,2011,36(8):1083-1086.
• [24]WEI H Y,GAO Z X,ZHENG L P,et al.Protective effects of fucoidan on aβ25-35 and d-gal-induced neurotoxicity in PC12 cells and d-gal-induced cognitive dysfunction in mice[J].Marine Drugs,2017,15(3):77.