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随着人类预期寿命的延长,人口老龄化问题日趋严重,阿尔兹海默症等神经退行性疾病的发病率也大幅上升[1]。学习记忆障碍作为阿尔兹海默症的主要临床表现之一,贯穿阿尔兹海默症疾病发展的全过程,并呈进行性加重,严重降低患者的生活质量,成为亟待解决的公共卫生问题[2]。海龙(Syngnathus)系为海龙科动物刁海龙Solenognathus hardwickii(Gy)、尖海龙Syngnathoides biaculeatus(Bloch)、拟海龙Syngnathus acus Linnaeus的干燥体,具有温肾壮阳、散结消肿的作用[3]。现代研究表明海龙富含多种脂肪酸、氨基酸以及甾体化合物,具有抗衰老、抗骨质疏松、性激素样等药理作用[4]。DHA作为海龙脂肪酸的重要成分之一,具有促进神经元细胞生长发育、抑制神经炎症及氧化应激的作用[5]。目前尚无治疗阿尔兹海默症的特效药物,海龙在改善学习记忆损伤方面的研究亦属空白。本研究拟探讨海龙对D-半乳糖诱导衰老小鼠学习记忆损伤的保护作用,并测定海龙中DHA含量,初步阐明海龙改善学习记忆损伤的作用机制。
Effect of traditional Chinese medicine Syngnathus on D-galactose-induced learning and memory impairment in aging mice
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摘要:
目的 研究中药海龙对D-半乳糖诱导衰老小鼠学习记忆损伤的影响及其作用机制。 方法 采用高效液相色谱(HPLC)技术测定海龙中抗学习记忆损伤有效成分二十二碳六烯酸(DHA)含量;腹腔注射D-半乳糖(D-gal)制备衰老小鼠模型,以Morris水迷宫实验及蛋白免疫印迹法等,对小鼠学习记忆能力、海马组织氧化损伤相关生化指标及蛋白表达进行检测,探究海龙对衰老小鼠学习记忆损伤的保护作用及其机制。 结果 HPLC结果显示,海龙中DHA含量为7.761 3 mg/g(以生药计),约占总成分的47%;Morris水迷宫实验结果显示,海龙可减少学习记忆损伤小鼠逃避潜伏期时间,增加小鼠目标象限游泳时间、游泳路程占比、穿台次数,改善小鼠学习记忆损伤;此外,海龙可激活衰老小鼠海马组织AKT/FOXO1/SOD2信号通路,上调氧化应激通路相关蛋白表达,降低衰老小鼠海马组织氧化损伤程度改善小鼠学习记忆损伤。 结论 本研究发现海龙富含二十二碳六烯酸,具有改善D-半乳糖诱导衰老小鼠学习记忆损伤的作用,并初步阐明其作用机制与抗氧化相关,为中药海龙抗学习记忆损伤研究提供了实验依据。 Abstract:Objective To study the effect of traditional Chinese medicine, Syngnathus on learning and memory impairment induced by D-galactose in aging mice and its mechanism of action. Methods HPLC was used to determine the content of DHA, the active ingredient in anti-learning and memory impairment in Syngnathus. The aging mouse model was prepared by intraperitoneal injection of D-galactose (D-gal). Morris water maze test and Western blot were used to detect the ability of learning and memory, biochemical indicators and protein expression related to oxidative damage in the hippocampus, and to explore the protective effect and mechanism of Syngnathus on learning and memory impairment in aging mice. Results HPLC results showed that the DHA content in Syngnathus was 7.761 3 mg/g (calculated as crude drug), accounting for about 47% of the total composition. Morris water maze results showed that Syngnathus could reduce the escape latency of learning and memory-impaired aging mice and increase the target quadrant swimming time, the proportion of swimming distance and the number of times of crossing the platform, and improve the learning and memory impairment of mice. In addition, Syngnathus can activate the AKT/FOXO1/SOD2 signaling pathway in the hippocampus of aging mice with learning and memory impairment, promote the expression of oxidative stress pathway-related proteins, and improve the learning and memory impairment in aging mice by reducing the degree of oxidative damage in the hippocampus of aging mice. Conclusion This study found that Syngnathus is rich in DHA, which has the effect of improving learning and memory impairment induced by D-galactose in aging mice, and preliminarily clarified that its mechanism of action is related to anti-oxidation. Experimental evidence is provided. -
Key words:
- Syngnathus /
- docosahexaenoic acid /
- D-galactose /
- learning and memory impairment /
- hippocampus /
- oxidative damage
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[1] SHARMA P, SHARMA A, FAYAZ F, et al. , Biological Signatures of Alzheimer's Disease[J]. Curr Top Med Chem,2020,20(9):770-781. doi: 10.2174/1568026620666200228095553 [2] WILSON R S, WANG T H, YU L, et al. Cognitive activity and onset age of incident Alzheimer disease dementia[J]. Neurology,2021,97(9):e922-e929. doi: 10.1212/WNL.0000000000012388 [3] 彭维兵, 唐旭利, 李国强, 等. 尖海龙与刁海龙化学成分及药理活性比较研究[J]. 中国海洋药物, 2010, 29(5):10-15. [4] 刘冬, 张红印, 鲍悦, 等. 海龙药理作用研究进展[J]. 吉林中医药, 2015, 35(10):1040-1042. [5] 史筱莉, 徐永健, 牟金婷, 等. 大海马和刁海龙氨基酸与脂肪酸的组成分析与评价[J]. 中国海洋药物, 2017, 36(2):75-83. [6] VATNER S F, ZHANG J, OYDANICH M, et al. Healthful aging mediated by inhibition of oxidative stress[J]. Ageing Res Rev,2020,64:101194. doi: 10.1016/j.arr.2020.101194 [7] BRIEGER K, SCHIAVONE S, MILLER F J Jr, et al. Reactive oxygen species: from health to disease[J]. Swiss Med Wkly,2012,142:w13659. [8] LOBO V, PATIL A, PHATAK A, et al. Free radicals, antioxidants and functional foods: impact on human health[J]. Pharmacogn Rev,2010,4(8):118-126. doi: 10.4103/0973-7847.70902 [9] INAL M E, KANBAK G, SUNAL E. Antioxidant enzyme activities and malondialdehyde levels related to aging[J]. Clin Chim Acta,2001,305(1-2):75-80. doi: 10.1016/S0009-8981(00)00422-8 [10] EICHENBAUM H. The role of the Hippocampus in navigation is memory[J]. J Neurophysiol,2017,117(4):1785-1796. doi: 10.1152/jn.00005.2017 [11] PRAJIT R, SRITAWAN N, SUWANNAKOT K, et al. Chrysin protects against memory and hippocampal neurogenesis depletion in D-galactose-induced aging in rats[J]. Nutrients,2020,12(4):E1100. doi: 10.3390/nu12041100 [12] SONG Y S, NARASIMHAN P, KIM G S, et al. The role of Akt signaling in oxidative stress mediates NF-kappaB activation in mild transient focal cerebral ischemia[J]. J Cereb Blood Flow Metab,2008,28(12):1917-1926. doi: 10.1038/jcbfm.2008.80 [13] MARTINS R, LITHGOW G J, LINK W. Long live FOXO: unraveling the role of FOXO proteins in aging and longevity[J]. Aging Cell,2016,15(2):196-207. doi: 10.1111/acel.12427 [14] AKASAKI Y, ALVAREZ-GARCIA O, SAITO M, et al. FoxO transcription factors support oxidative stress resistance in human chondrocytes[J]. Arthritis Rheumatol,2014,66(12):3349-3358. doi: 10.1002/art.38868 [15] YAMAGATA K. Dietary docosahexaenoic acid inhibits neurodegeneration and prevents stroke[J]. J Neurosci Res,2021,99(2):561-572. doi: 10.1002/jnr.24728 [16] OGURO A, FUJITA K, ISHIHARA Y, et al. DHA and its metabolites have a protective role against methylmercury-induced neurotoxicity in mouse primary neuron and SH-SY5Y cells[J]. Int J Mol Sci,2021,22(6):3213. doi: 10.3390/ijms22063213 [17] BECERIR C, KıLıÇ İ, SAHIN Ö, et al. The protective effect of docosahexaenoic acid on the bilirubin neurotoxicity[J]. J Enzyme Inhib Med Chem,2013,28(4):801-807. doi: 10.3109/14756366.2012.684053 [18] CHANG C Y, KUAN Y H, LI J R, et al. Docosahexaenoic acid reduces cellular inflammatory response following permanent focal cerebral ischemia in rats[J]. J Nutr Biochem,2013,24(12):2127-2137. doi: 10.1016/j.jnutbio.2013.08.004