姬松茸多糖对D-半乳糖诱导的衰老模型小鼠的抗衰老作用及其Keap1/Nrf2/ARE信号转导途径机制

doi:10.13481/j.1671-587x.20200223

吉林大学学报(医学版) ›› 2020, Vol. 46 ›› Issue (02): 346-351.doi: 10.13481/j.1671-587x.20200223

• 基础研究 • 上一篇

姬松茸多糖对D-半乳糖诱导的衰老模型小鼠的抗衰老作用及其Keap1/Nrf2/ARE信号转导途径机制

段懿涵, 盛瑜, 徐健, 卢学春, 杜培革, 安丽萍

北华大学药学院药物分析教研室, 吉林吉林 132013

收稿日期:2019-12-05 发布日期:2020-04-07
通讯作者: 安丽萍,教授,硕士研究生导师(Tel:0432-64608287,E-mail:alp960@126.com);杜培革,教授,硕士研究生导师(Tel:0432-64608287,E-mail:dupeige2001@126.com) E-mail:alp960@126.com;dupeige2001@126.com
作者简介:段懿涵(1995-),女,吉林省通化市人,在读医学硕士,主要从事药物分析学方面的研究。
基金资助:
吉林省中医药管理局科研基金资助课题（2019128）；吉林省发改委科研基金资助课题（2018C046-3）；吉林省卫健委科研基金资助课题（2017J083）；北华大学北华研创科研基金资助课题[合字（2019）第063号]

Anti-aging effects of Agaricus blazei polysaccharide in D-galactose-induced aging model mice and Keap1/Nrf2/ARE signal transduction pathway mechanism

DUAN Yihan, SHENG Yu, XU Jian, LU Xuechun, DU Peige, AN Liping

Department of Pharmaceutical Analysis, College of Pharmacy, Beihua University, Jilin 132013, China

Received:2019-12-05 Published:2020-04-07

摘要/Abstract

摘要： 目的：研究姬松茸酸性多糖A级分（ABP-A）对D-半乳糖（D-Gal）所致衰老模型小鼠的抗衰老作用，并探讨姬松茸多糖（ABP）的抗衰老机制。方法：水提醇沉法提取姬松茸粗多糖，并进行DEAE-纤维素离子交换柱层析分级及成分分析，得到ABP-A。48只ICR雄性小鼠随机分为对照组、模型组、阳性药物（吡拉西坦）组和ABP-A组，每组12只。给药70 d后进行小鼠Morris水迷宫、避暗和跳台行为学实验；检测各组小鼠血清中超氧化物歧化酶（SOD）活性、丙二醛（MDA）水平、总抗氧化能力（T-AOC）、过氧化氢酶（CAT）活性和活性氧（ROS）水平，Western blotting法检测各组小鼠脑组织中Nrf2、Keap1和HO-1蛋白表达水平。结果：ABP的总糖含量为75.1%，DEAE-纤维素离子交换柱层析分级得到ABP-A。行为学实验，与模型组比较，ABP-A组小鼠避暗潜伏期明显延长（P<0.05），错误次数明显减少（P<0.05），跳台潜伏期明显延长（P<0.05），错误次数明显减少（P<0.05），定位航行潜伏期明显缩短（P<0.05），进入平台次数明显增加（P<0.05）。生化指标检测，与模型组比较，ABP-A组小鼠血清中SOD和CAT活性升高（P<0.05），T-AOC升高（P<0.05），MDA和ROS水平降低（P<0.05）。Western blotting法，与模型组比较，ABP-A组小鼠脑组织中HO-1蛋白表达水平升高（P<0.05），Nrf2和Keap1蛋白表达水平降低（P<0.05或P<0.01）。结论：ABP可改善衰老模型小鼠学习记忆能力，其机制可能与调节以Nrf2为核心的Keap1/Nrf2/ARE氧化应激通路相关因子Nrf2、Keap1和HO-1发挥抗衰老作用有关。

关键词: 姬松茸多糖, 抗衰老, 学习记忆能力, Keap1/Nrf2/ARE信号通路

Abstract: Objective: To study the anti-aging effect of Agaricus blazei polyssaccharide-A (ABP-A) in the aging model mice induced by D-galactose (D-Gal), and to explore the anti-aging mechanism of Agaricus blazei polysaccharide(ABP). Methods: The crude polysaccharide from Agaricus blazei Murill(ABM) was extracted by water extraction and alcohol precipitation, and the fractions were analyzed by DEAE-cellulose ion exchange column chromatography;ABP-Awas obtained.A total of 48 male ICR mice were randomly divided into control group, model group, positive drug group(Piracetam)and ABP-A group(n=12). Morris water maze, dark avoidance and platform jumping behavior experiments were performed at 70 d after administration. The superoxide dismutase (SOD) activitives, the malondialdehyde (MDA) levels,the total antioxidant capacities (T-AOC), the catalase (CAT) activitives, and the reactive oxygen species (ROS) levels in serum of the mice in various groups were detected. Western blotting method was used to detect the expression levels of Nrf2, Keap1 and HO-1 proteins in the brain tissue of the mice in various groups. Results: The total sugar content of ABP was 75.1%. The ABP-A was graded and gained by DEAE-cellulose ion exchange column chromatography.The behavioral experiment results showed that compared with model group, the dark avoidance latency of the mice in ABP-A group was significantly lengthened (P<0.05), the number of errors was decreased significantly (P<0.05); the latency of step down was significantly prolonged (P<0.05), and the number of errors was decreased significantly (P<0.05); the positioning latency of the mice in ABP-A group was significantly shortened(P<0.05), and the number of entering to the platform was increased significantly (P<0.05). Compared with model group, the activities of serum SOD and CAT of the mice in ABP-A group were increased(P<0.05),the T-AOC was increased(P<0.05), the levels of MDA and ROS were decreased(P<0.05).The Western blotting results showed that compared with model group, the expression level of HO-1 protein in the brain tissue of the mice in ABP-A group was increased (P<0.05), and the expression levels of Nrf2 and Keap1 proteins were decreased (P<0.05 or P<0.01). Conclusion: ABP can improve the learning and memory ability of the aging model mice, and its mechanism may be related to regulating Keap1/Nrf2/ARE oxidative stress pathway related factors Nrf2, Keap1, and HO-1 with Nrf2 as the core to perform the anti-aging effect.

Key words: Agaricus blazei polysaccharide, anti-aging, learning and memory ability, Keap1/Nrf2/ARE signal pathway

中图分类号:

R339.38

段懿涵, 盛瑜, 徐健, 卢学春, 杜培革, 安丽萍. 姬松茸多糖对D-半乳糖诱导的衰老模型小鼠的抗衰老作用及其Keap1/Nrf2/ARE信号转导途径机制[J]. 吉林大学学报(医学版), 2020, 46(02): 346-351.

DUAN Yihan, SHENG Yu, XU Jian, LU Xuechun, DU Peige, AN Liping. Anti-aging effects of Agaricus blazei polysaccharide in D-galactose-induced aging model mice and Keap1/Nrf2/ARE signal transduction pathway mechanism[J]. Journal of Jilin University(Medicine Edition), 2020, 46(02): 346-351.

参考文献

[1] LI H D,ZHAO H J,GAO Z, et al. Pleurotus djamor the antioxidant and anti-aging effects of acetylated mycelia polysaccharides from[J].Molecules, 2019, 24(15):2698.
[2] UR R S, ALI S S, TAHIR A,et al. Anthocyanins reversed D-galactose-induced oxidative stress and neuroinflammation mediated cognitive impairment in adult rats[J]. Mol Neurobiol, 2017, 54:255-271.
[3] SFEIR A J, CHAI W, SHAY J W. Telomereend processing the terminal nucleotides of human chromosomes[J]. Mol Cell, 2005, 18(1):131-138.
[4] FRAUKE B, SHAHRZAD K M, JURGEN K, et al. A metabolic Obesity Profile is associated with decreased gray matter volume in cognitively healthy older adults[J].Front Aging Neurosci, 2019, 11:202.
[5] DRUZIAN S P,PINHEIRO L N,SUSIN N M,et al. Production of metabolites with antioxidant activity by Botryosphaeria dothidea in submerged fermentation[J]. Bioprocess Biosystems Engineer, 2020,43(1):13-20.
[6] VEERAPPAN V G, MUTHU R,et al. Agaricus blazei extract abrogates rotenone-induced dopamine depletion and motor deficits by its anti-oxidative and anti-inflammatory properties in Parkinsonic mice[J].Nutr Neurosci, 2018, 21:657-666.
[7] 王夏梅. 姬松茸子实体多糖分离纯化、结构表征和免疫活性分析[D].无锡:江南大学,2016.
[8] JIANG L Y,YU Z P,LIN Y,et al. Agaricus blazeiLow-molecular-weight polysaccharides from Murrill modulate the Th1 response in cancer immunity[J].Oncol Lett, 2018, 15:3429-3436.
[9] 安丽萍,段懿涵,盛瑜,等.姬松茸多糖酶降解对D-半乳糖诱导3T3细胞氧化损伤的保护作用[J].北华大学学报(自然科学版),2019,20(5):653-658.
[10] ZHAO S S, YANG W, JIN H, et al. Puerarin attenuates learning and memory impairments and inhibits oxidative stress in STZ-induced SAD mice[J].Neurotoxicology, 2015, 51:166-171.
[11] ZHANG H H, ZHENG W, FENG X L, et al. Nrf2/ARE signaling Acts as master pathway for the cellular antioxidant activity of fisetin.[J].Molecules, 2019, 24(4):708.
[12] SADIGH E S, MAJDI A, MCCANN S K,et al. D-galactose-induced brain ageing model:A systematic review and meta-analysis on cognitive outcomes and oxidative stress indices[J]. PLoS One, 2017, 12(8):e0184122.
[13] ISLAM M T. Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders[J]. Neurol Res, 2017, 39(1):73-82.
[14] SUN X, SUN G B, WANG M,et al. Protective effects of cynaroside against H2O2induced apoptosis in H9c2 cardiomyoblasts[J]. J Cell Biochem, 2011,112(8):2019-2029.
[15] HE H B, XU J, XU Y Q,et al. Cardioprotective effects of saponins from Panax japonicus on acute myocardial ischemia against oxidative stresstriggered damage and cardiac cell death in rats[J]. J Ethnopharmacol,2012,140(1):73-82.
[16] SINGH C K,CHHABRA G,NDIAYE M,et al.The role of sirtuins in antioxidant and redox signaling[J]. Antioxid Redox Signal,2018,28(8):643-661.
[17] WANG Z,JI C Y,WU L Y, et al. Tert-butylhydroquinone alleviates early brain injury and cognitive dysfunction after experimental subarachnoid hemorrhage:role of Keap1/Nrf2/ARE pathway[J].PLoS One, 2014, 9:e97685.
[18] KUBBEN N, ZHANG W, WANG L, et al. Repression of the antioxidant NRF2 pathway in premature aging[J]. Cell, 2016, 165(6):1361-1374.
[19] MAHMOUD A M, GERMOUSH M O, ALOTAIBI M F,et al. Possible involvement of Nrf2 and PPARγ up-regulation in the protective effect of umbelliferone against cyclophosphamide-induced hepatotoxicity[J]. Biomed Pharmacother, 2016, 86:297-306.
[20] ZHANG L, WANG H D, FAN Y W, et al. Fucoxanthin provides neuroprotection in models of traumatic brain injury via the Nrf2-ARE and Nrf2-autophagy pathways[J].Sci Rep, 2017, 7:46763.
[21] YA B L, LIU Q, LI H F, et al. Uric acid protects against focal cerebral ischemia/reperfusion-induced oxidative stress via activating Nrf2 and regulating neurotrophic factor expression[J].Oxid Med Cell Longev, 2018, 2018:6069150.

姬松茸多糖对D-半乳糖诱导的衰老模型小鼠的抗衰老作用及其Keap1/Nrf2/ARE信号转导途径机制

Anti-aging effects of Agaricus blazei polysaccharide in D-galactose-induced aging model mice and Keap1/Nrf2/ARE signal transduction pathway mechanism

RichHTML

PDF (PC)

赞

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 4

Metrics

本文评价

推荐阅读 0

[1]	魏洁, 李开济, 赵毓芳, 骆广玲, 魏静波, 闫丰, 吕翠平, 甄永占. 赖氨大黄酸对D-半乳糖致衰老模型小鼠的肾脏保护作用及其作用机制[J]. 吉林大学学报(医学版), 2015, 41(04): 680-684.
[2]	罗翔丹\|姚刚\|张铁华. 3种真菌多糖对嗜酸乳杆菌发酵特性的影响[J]. J4, 2011, 37(6): 1047-1050.
[3]	郝利铭，姜文华，董智勇，孟晓婷. 红鹿制剂延缓皮肤老化的研究[J]. J4, 2005, 31(5): 709-712.
[4]	崔云山，徐华丽，于小风，曲绍春. 芝麻素散剂抗衰老作用的药理学研究[J]. J4, 2005, 31(3): 411-413.