原花青素对淀粉样蛋白Aβ25-35诱导的SH-SY5Y细胞毒性的影响

doi:10.3969/j.issn.1004-616x.2017.02.003

癌变·畸变·突变 ›› 2017, Vol. 29 ›› Issue (2): 91-95.doi: 10.3969/j.issn.1004-616x.2017.02.003

原花青素对淀粉样蛋白Aβ_25-35诱导的SH-SY5Y细胞毒性的影响

周亚盼^1,2, 张小强^1,2, 曲志华^1,2, 张妍^1,2, 梁晓瑜^1,2

1. 东南大学公共卫生学院, 江苏南京 210009;
2. 东南大学环境医学工程教育部重点实验室, 江苏南京 210009

收稿日期:2017-01-09 修回日期:2017-02-28 出版日期:2017-03-31 发布日期:2017-03-31
通讯作者: 张小强,E-mail:zhangxq7843@126.com E-mail:zhangxq7843@126.com
作者简介:周亚盼,E-mail:blackeyes023@163.com。
基金资助:
2016年江苏省普通高校研究生科研创新计划资助项目资助（SJZZ16_0034）；江苏省卫生厅预防医学科研基金（Y2013070）

The influences of proanthocyanidin on amyloid beta fragment Aβ_25-35 induced cytotoxicity in SH-SY5Y cells

ZHOU Yapan^1,2, ZHANG Xiaoqiang^1,2, QU Zhihua^1,2, ZHANG Yan^1,2, LIANG Xiaoyu^1,2

1. School of Public Health, Southeast University, Nanjing 210009;
2. Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Southeast University, Nanjing 210009, Jiangsu, China

Received:2017-01-09 Revised:2017-02-28 Online:2017-03-31 Published:2017-03-31

摘要/Abstract

摘要：

目的：探讨原花青素对淀粉样蛋白片段Aβ_25-35染毒的SH-SY5Y细胞存活、氧化应激及其分泌淀粉样蛋白Aβ_1-42和可溶性淀粉样蛋白sAPPα水平的影响。方法：分别以不同浓度（0.1、0.5、1.0、5.0 μg/mL）原花青素和不同浓度（0.1、1.0、10.0、20.0 μmol/L）的Aβ_25-35作用SH-SY5Y细胞24 h后用MTT法检测细胞活力，进一步以1.0 μmol/L Aβ_25-35染毒细胞，建立细胞损伤模型，不同浓度（0.1、0.5、1.0、5.0 μg/mL）原花青素干预24 h，用MTT法检测细胞活力，ELISA法检测细胞分泌Aβ_1-42水平及sAPPα水平，TBA法测定细胞内丙二醛（MDA）含量，WST-8法测定细胞内总超氧化物歧化酶（SOD）活力。结果：与对照组相比，不同浓度原花青素作用24 h后，细胞存活率差异均无统计学意义（P均>0.05），而不同浓度Aβ_25-35均使SH-SY5Y细胞活力降低（P < 0.01），其中1.0 μmol/L Aβ_25-35 对细胞活力的抑制作用最强（P < 0.01）。以1.0 μmol/L Aβ_25-35染毒细胞，Aβ_1-42分泌水平升高（P < 0.01），sAPPα水平降低（P < 0.01），细胞内MDA含量升高（P < 0.01），总SOD活力降低（P < 0.01）。与1.0 μmol/L Aβ_25-35染毒组比较，0.1、0.5、1.0、5.0 μg/mL原花青素干预可提高各组细胞活力（P < 0.05），降低Aβ_1-42分泌水平（P < 0.01）；0.5、1.0、5.0 μg/mL原花青素干预可提高细胞分泌sAPPα水平（P < 0.05），降低细胞内MDA含量（P < 0.05），增强总SOD活力（P < 0.05）。结论：原花青素可减轻Aβ_25-35诱导的SH-SY5Y细胞Aβ负荷，并减轻细胞氧化损伤。

关键词: 原花青素, Aβ_1-42, sAPPα, 细胞毒性

Abstract:

OBJECTIVE: The influence of proanthocyanidins on oxidative stress,secretion of amyloid protein Aβ_1-42 and soluble amyloid precursor protein sAPPα which were induced by amyloid protein fragment Aβ_25-35 in SH-SY5Y cells was investigated. METHODS: SH-SY5Y cells were treated with Aβ_25-35 of different concentrations (0.1,1.0,10.0 and 20.0 μmol/L) for 24 hours. Cell viability was measured by MTT assay. Cell injury models were built with 1.0 μmol/L Aβ_25-35,with proanthocyanidin of different concentrations added to cell cultures and incubated for 24 h. Concentrations of Aβ_1-42 and sAPPα in cell supernatant were determined by using ELISA. Intracellular content MDA and total SOD were determined by the method of TBA test and WST-8,respectively. RESULTS: Compared with the control group,cells treated with Aβ_25-35 (1 μmol/L) had significantly declined cell viability (P < 0.01),increased Aβ_1-42 level (P < 0.01),declined sAPPα concentration (P < 0.01),increased intracellular MDA content (P < 0.01),and decreased total SOD vitality (P < 0.01). Compared with the Aβ_25-35 injury cell models,proanthocyanidin (0.1,0.5,1.0 and 5.0 μg/mL) significantly improved cell viability (P < 0.05),decreased the secretion of Aβ_1-42 (P < 0.01). Proanthocyanidin (0.5,1.0 and 5.0 μg/mL) increased sAPPα concentration (P < 0.05),decreased MDA content (P < 0.05),and strengthened total SOD vitality (P < 0.05). CONCLUSION: Proanthocyanidin alleviated the Aβ burden and oxidative stress in SH-SY5Y cells which were induced by Aβ_25-35.

Key words: proanthocyanidin, Aβ_1-42, sAPPα, cytotoxicity

中图分类号:

R329.2+8

周亚盼, 张小强, 曲志华, 张妍, 梁晓瑜. 原花青素对淀粉样蛋白Aβ_25-35诱导的SH-SY5Y细胞毒性的影响[J]. 癌变·畸变·突变, 2017, 29(2): 91-95.

ZHOU Yapan, ZHANG Xiaoqiang, QU Zhihua, ZHANG Yan, LIANG Xiaoyu. The influences of proanthocyanidin on amyloid beta fragment Aβ_25-35 induced cytotoxicity in SH-SY5Y cells[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2017, 29(2): 91-95.

参考文献

[1] CHAN K Y,WANG W,WU J J,et al. Epidemiology of Alzheimer's disease and other forms of dementia in China,1990-2013;2010:a systematic review and analysis[J]. Lancet,2013,381(9882):2016-2023.

[2] 李梦秋,张文武,陈涛,等. 阿尔茨海默病药物治疗临床证据评价[J]. 中国现代神经疾病杂志,2014,(3):192-197.

[3] BALLARD C,GAUTHIER S,CORBETT A,et al. Alzheimer's disease[J]. Lancet,2011,377(9770):1019-1031.

[4] 赵绪韬,傅毅,董文心. β淀粉样蛋白靶向药物治疗阿尔茨海默病的研究进展[J]. 世界临床药物,2013,34(1):49-54.

[5] 陈金枝,张小强,曲志华,等. 原花青素对脂多糖诱导BV2 小胶质细胞炎症介质分泌的影响[J]. 癌变·畸变·突变,2016,28(3):214-217.

[6] LEE T,KWON H S,BANG B R,et al. Grape seed proanthocyanidin extract attenuates allergic inflammation in murine models of asthma[J]. J Clin Immunol,2012,32(6):1292-1304.

[7] JHUN J Y,MOON S J,YOON B Y,et al. Grape seed proanthocyanidin extract-mediated regula-tion of STAT3 proteins contributes to Treg differentiation and attenuates inflammation in a murine model of obesity-associated arthritis[J]. PLoS One,2013,8(11):78843.

[8] ESPOSITO D,CHEN A,GRACE M H,et al. Inhibitory effects of wild blueberry anthocyanins and other flavonoids on biomarkers of acute and chronic inflammation in vitro[J]. J Agric Food Chem,2014,62(29):7022-7028.

[9] HABCHI J,CHIA S,LIMBOCKER R,et al. Systematic development of small molecules to inhibit specific microscopic steps of Aβ₄₂ aggregation in Alzheimer's disease[J]. Proc Natl Acad Sci U S A,2017,114(2):200-208.

[10] FRANCA M B,LIMA K C,ELEUTHERIO E C. Oxidative stress and amyloid toxicity:insights from yeast[J]. J Cell Biochem,2016,doi:10.1002/jcb.25803.

[11] OMTRI R S,DAVIDSON M W,ARUMUGAM B,et al. Differences in the cellular uptake and intracellular itineraries of amyloid beta proteins 40 and 42:ramifications for the Alzheimer's drug discovery[J]. Mol Pharm,2012,9(7):1887-1897.

[12] MILLS J,REINER P B. Regulation of amyloid precursor protein cleavage[J]. J Neurochem,1999,72(2):443-457.

[13] CHAKROBORTY S,STUTZMANN G E. Calcium channelo-pathies and Alzheimer's disease:insight into therapeutic success and failures[J]. Eur J Pharmacol,2014,739:83-95.

[14] LOVELL M A,EHMANN W D,BUTLER S M,et al. Elevated thiobarbituric acid-reactive substances and antioxidant enzyme activity in the brain in Alzheimer's disease [J]. Neurology,1995,45(8):1594-1601.

[15] LOVELL M A,ROBERTSON J D,TEESDALE W J,et al. Copper,iron and zinc in Alzheimer's disease senile plaques[J]. J Neurol Sci,1998,158(1):47-52.

[16] KANNO H,KAWAKAMI Z,TABUCHI M,et al. Protective effects of glycycoumarin and procyanidin B1,active components of traditional Japanese medicine yokukansan,on amyloid beta oligomer-induced neuronal death[J]. J Ethno-pharm,2015,159:122-128.

[17] PORAT Y,ABRAMOWITZ A,GAZIT E. Inhibition of amyloid fibril formation by polyphenols:structural similarity and aromatic interactions as a common in-hibition mechanism [J]. Chem Biol Drug Des,2006,67(1):27-37.

[18] TODA T,SUNAGAWA T,KANDA T,et al. Apple procyanidins suppress amyloid beta-protein aggregation[J]. Biochem Res Int,2011,2011:784698-784706.

[19] XIE H,WANG J R,YAU L F,et al. Catechins and procyanidins of Ginkgo biloba show potent activities towards the inhibition of beta-amyloid peptide aggregation and destabili-zation of preformed fibrils[J]. Molecules,2014,19(4):5119-5134.

[20] LIAN Q W,NIE Y S,ZHANG X Y,et al. Effects of grape seed proanthocyanidin on Alzheimer's disease in vitro and in vivo[J]. Exp Ther Med,2016,12(3):681-1692.

[21] 蔡洪斌,王峰,张义军. 原花青素对阿尔茨海默病模型大鼠脑组织的预防保护作用[J]. 中国老年学杂志,2011,31(22):4408-4410.

[22] 马玉红,窦德宇,柳春燕,等. 原花青素对体外阿尔茨海默病的预防作用[J]. 皖南医学院学报,2014,41(3):199-201.

原花青素对淀粉样蛋白Aβ_25-35诱导的SH-SY5Y细胞毒性的影响

The influences of proanthocyanidin on amyloid beta fragment Aβ_25-35 induced cytotoxicity in SH-SY5Y cells

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原花青素对淀粉样蛋白Aβ25-35诱导的SH-SY5Y细胞毒性的影响

The influences of proanthocyanidin on amyloid beta fragment Aβ25-35 induced cytotoxicity in SH-SY5Y cells

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原花青素对淀粉样蛋白Aβ_25-35诱导的SH-SY5Y细胞毒性的影响

The influences of proanthocyanidin on amyloid beta fragment Aβ_25-35 induced cytotoxicity in SH-SY5Y cells