目的 探讨远志寡糖酯抗β淀粉样蛋白25-35诱导SH-SY5Y细胞损伤的作用及相关机制。方法 不同浓度的远志寡糖酯与SH-SY5Y细胞孵育1 h,再与25 μmol·L-1的β Amyloid Fragment25-35(Aβ25-35)共同孵育24 h。四甲基偶氮唑蓝(MTT)法检测细胞存活率;流式细胞仪检测细胞凋亡;生化法测定细胞上清液中乳酸脱氢酶(LDH)含量及细胞内超氧化物歧化酶(SOD)活性和丙二醛(MDA)的含量;Western blot检测胞内凋亡相关蛋白Bcl-2和Bax的表达。结果 远志寡糖酯能够显著提高Aβ25-35损伤的SH-SY5Y细胞存活率,降低细胞凋亡率,减少细胞LDH释放,增加胞内SOD活性并降低MDA含量,增加抗凋亡蛋白Bcl-2的表达,降低凋亡蛋白Bax的表达。结论 远志寡糖酯能够对抗Aβ25-35诱导的SH-SY5Y细胞损伤,与抗氧化损伤和减少细胞凋亡有关。
Abstract
OBJECTIVE To investigate the effects of oligosaccharide esters of Polygala tenuifolia on Aβ25-35 induced injury in SH-SY5Y cells and the relative mechanisms. METHODS SH-SY5Y cells were cultured with Aβ25-35(25 μmol·L-1) for 24 h in the presence and absence of oligosaccharide esters component of Polygala tenuifolia. The cell viability was measured by MTT method; cell apoptosis was detected by flow cytometry; the LDH release, the SOD activity and MDA level were measured by biochemistry method; the Bcl-2 and Bax expression were determined by Western blotting. RESULTS Oligosaccharide esters of Polygala tenuifolia could enhance the cell viability, decrease the apoptotic rate, the release of LDH and MDA level, and increase SOD activity. It also enhanced the expression of anti-apoptotic protein Bcl-2 and decreased the expression of apoptotic protein Bax. CONCLUSION Oligosaccharide esters of Polygala tenuifolia have neuroprotective effects against the Aβ25-35 induced injury in SH-SY5Y cells, which is related to its anti-oxidation and anti-apoptosis.
关键词
远志寡糖酯 /
β淀粉样蛋白 /
细胞凋亡 /
氧化应激
{{custom_keyword}} /
Key words
oligosaccharide esters of Polygala tenuifolia /
β-amyloid protein /
cell apoptosis /
oxidative stress
{{custom_keyword}} /
中图分类号：
R965
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] PHILLIPS C. Alzheimer′s disease care:costs and potential savings[J]. J Am Geriatr Soc, 1999, 47(9):1163-1165.
[2] ALZHEIMER′S A. 2015 Alzheimer′s disease facts and figures[J]. Alzheimers Dement, 2015, 11(3):332-384.
[3] KUMAR A,SINGH A. A review on Alzheimer′s disease pathophysiology and its management:an update[J]. Pharmacol Rep, 2015, 67(2):195-203.
[4] HARRISON J R, OWEN M J. Alzheimer′s disease:the amyloid hypothesis on trial[J]. Br J Psychiatry,2016, 208(1):1-3.
[5] ZHANG T Z, RONG W W, LI Q,et al. Research progress of Polygalaceae[J]. Chin Tradit Herb Drugs(中草药), 2016,47(13):2381-2389.
[6] HUANG S M,QIAN S Y,WANG N,et al. Research progress on central pharmacological activities of oligosaccharide esters in Polygala tenuifolia[J]. J Liaoning Univ Tradit Chin Med(辽宁中医药大学学报), 2016,18(8):5-7.
[7] Ch.P(2015)VolⅠ(中国药典2015年版.一部) [S].2015:157.
[8] WANG R,PEI W H,FANG F. Effect of oligosaccharide esters in Polygala tenuifolia on improvement of scopolamine-induced learning and memory obstacles in rats[J]. J Liaoning Univ Tradit Chin Med(辽宁中医药大学学报), 2016,18(4):10-13.
[9] ABARIKWU S O, FAROMBI E O. Atrazine induces apoptosis of SH-SY5Y human neuroblastoma cells via the regulation of Bax/Bcl-2 ratio and caspase-3-dependent pathway[J]. Pest Biochem Physiol, 2015, 118:90-98.
[10] STHR J, WATTS J C, MENSINGER Z L, et al. Purified and synthetic Alzheimer′s amyloid beta(Aβ) prions[J]. Proc Natl Acad Sci USA, 2012, 109(27):11025-11030.
[11] PIKE C J, WALENCEWICZ-WASSERMAN A J, KOSMOSKI J, et al. Structure-activity analyses of β-amyloid peptides:contributions of the β25-35 region to aggregation and neurotoxicity[J]. J Neurochem,1995,64(1):253-265.
[12] FROZZA R L, HORN A P, HOPPE J B, et al. A comparative study of β-amyloid peptides Aβ1-42 and Aβ25-35 toxicity in organotypic hippocampal slice cultures[J]. Neurochem Res, 2009,34(2):295-303.
[13] OLTVAL Z N, MILLIMAN C L, KORSMEYER S J. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell death[J]. Cell, 1993, 74(4):609-619.
[14] CAI Z, ZHAO B, RATKA A. Oxidative stress and β-amyloid protein in Alzheimer′s disease[J]. Neuromol Med, 2011, 13(4):223-250.
[15] BRADLEY-WHITMAN M A, LOVELL M A. Biomarkers of lipid peroxidation in Alzheimer disease(AD):an update[J]. Arch Toxicol, 2015, 89(7):1035-1044.
[16] ARIMON M, TAKEDA S, POST K L, et al. Oxidative stress and lipid peroxidation are upstream of amyloid pathology[J]. Neurobiol Dis, 2015, 84:109-119.
[17] QIAN X, CAO H, MA Q, et al. Allopregnanolone attenuates Aβ25-35-induced neurotoxicity in PC12 cells by reducing oxidative stress[J]. Int J Clin Exp Med, 2015, 8(8):13610-13615.
[18] TIAN X, GUO L P, HU X L, et al. Protective effects of Arctium lappa L. roots against hydrogen peroxide-induced cell injury and potential mechanisms in SH-SY5Y cells[J]. Cell Mol Neurobiol, 2015, 35(3):335-344.
[19] YUAN M,WANG C L,WANG Y F, et al. Research progress of superoxide dismutase[J]. Chin J Histochem Cytochem(中国组织化学与细胞化学杂志), 2016,25(6):550-558.
[20] HU Y, LI J, LIU P, et al. Protection of SH-SY5Y neuronal cells from glutamate-induced apoptosis by 3,6′-disinapoyl sucrose, a bioactive compound isolated from radix polygala[J]. Biomed Res Int, 2012, 2012:1-5.
[21] LIU P, HU Y, GUO D H, et al. Antioxidant activity of oligosaccharide ester extracted from Polygala tenuifolia roots in senescence-accelerated mice[J]. Pharm Biol, 2010, 48(7):828-833.
[22] LIU X, WANG X, LU J. Tenuifoliside A promotes neurite outgrowth in PC12 cells via the PI3K/AKT and MEK/ERK/CREB signaling pathways[J]. Mol Med Rep, 2015, 12(5):7637-7642.
[23] LI C J, YANG J Z, YU S S, et al. Triterpenoid saponins and oligosaccharides from the roots of Polygala tenuifolia Willd[J]. Chin J Nat Med(中国天然药物), 2011, 9(5):321-328.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
基金
国家自然科学基金面上项目资助(81373995)
{{custom_fund}}
PDF(2166 KB)
