«上一篇/Previous Article|本期目录/Table of Contents|下一篇/Next Article»

《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

30卷

期数:

2024年01期

页码:

35-39

栏目:

基础医学

出版日期:

2024-01-01

文章信息/Info

Title:

Astaxanthin improves cardiac tissue damage in rapidly aging mice through autophagy

文章编号:

1006-8147(2024)01-0035-05

作者:

靳可青; 刘银玥; 王萌; 张绪梅

（天津医科大学公共卫生学院营养与食品卫生学系，天津300070）

Author(s):

JIN Keqing; LIU Yinyue; WANG Meng; ZHANG Xumei

（Department of Nutrition and Food Science，School of Public Health，Tianjin Medical University，Tianjin 300070，China）

关键词:

虾青素; SAMP10小鼠; 心脏组织; 自噬

Keywords:

astaxanthin; SAMP10 mice; cardiac tissue; autophagy

分类号:

R151

DOI:

10.20135/j.issn.1006-8147.2024.01.0035

文献标志码:

A

摘要:

目的：研究虾青素对快速老化小鼠心脏组织形态以及纤维化的影响，并探讨自噬及氧化应激在其中的作用。方法：将8只正常老化小鼠（SAMR1）作为正常对照组。将56只快速老化小鼠（SAMP10）随机分为模型对照组（16只）、虾青素低剂量[0.4 mg/（g·d）]干预组（8只）、虾青素中剂量[0.8 mg/（g·d）]干预组（16只）、虾青素高剂量[1.6 mg/（g·d）]干预组（8只）和虾青素中剂量加3-甲基腺嘌呤（3-MA）抑制剂组 （8只）。苏木精-伊红 （HE） 染色法检测小鼠心脏组织细胞形态改变。Masson染色检测小鼠心肌组织纤维化程度。比色法检测血浆和心脏组织中氧化应激指标丙二醛（MDA）和超氧化物歧化酶（SOD）的水平。蛋白免疫印迹检测各组小鼠心脏组织微管相关蛋白1轻链3（LC3）和自噬效应蛋白（Beclin-1）的表达。结果：与SAMR1组相比，SAMP10模型对照组小鼠心肌细胞纤维疏松、排列紊乱、纤维化严重；血浆和心脏组织MDA水平显著升高、SOD活力显著降低、心脏组织LC3和Beclin-1蛋白表达显著降低（F=23.73、9.43、7.04、14.81、13.73、15.38，均P<0.05）。与SAMP10模型对照组相比，虾青素干预后SAMP10小鼠心肌组织形态及纤维化显著改善；血浆和心脏组织MDA水平显著降低，SOD活力显著升高，心肌组织LC3和Beclin-1蛋白表达均显著增加（均P<0.05），且高剂量改善作用最为明显；与中剂量虾青素干预组相比，中剂量虾青素加3-MA抑制剂组心脏纤维化程度升高，血浆和心脏组织MDA水平升高、SOD活力降低、心脏组织LC3和Beclin-1蛋白表达降低（F=18.75、6.353、15.77、14.08、22.83、8.657，均P<0.05）。结论：虾青素通过增强自噬、降低氧化应激，从而改善SAMP10衰老小鼠心脏组织损害。

Abstract:

Objective： To investigate the effect of astaxanthin on cardiac morphology and fibrosis in rapidly aging mice，and to explore the role of autophagy and oxidative stress. Methods： Eight normal aging mice （SAMR1） were used as normal control group. 56 rapidly aging mice（SAMP10） were randomly divided into model control group（16 mice），astaxanthin low-dose[0.4 mg/（g·d）] group（8 mice）， astaxanthin medium-dose [0.8 mg/（g·d）] group （16 mice），and astaxanthin high-dose [1.6 mg/（g·d）] group （8 mice） and astaxanthin medium dose plus 3-MA inhibitor group（8 mice）. Hematoxylin-eosin（HE） staining was used to detect the morphological changes of mouse heart tissues. Masson staining was used to detect the degree of myocardial fibrosis. The levels of oxidative stress indexes such as malondialdehyde（MDA） and superoxide dismutase（SOD） in plasma and heart tissue were detected by colorimetry. The expressions of microtubule associated protein 1，light chain 3 （LC3） and autophagy effector protein 1 （Beclin-1） in heart tissue were detected by Western blotting. Results： Compared with SAMR1 group，SAMP10 model control group showed loose cardiomyocyte fibers， disordered arrangement，increased fibroblasts，severe fibrosis，and significantly increased MDA levels in plasma and heart tissue，SOD activity significantly decreased，LC3 and Beclin-1 protein expression in heart tissue were significantly decreased（F=23.73，9.43，7.04，14.81，13.73，15.38，all P<0.05）. However， compared with the SAMP10 model control group，the myocardial morphology and fibrosis were significantly improved，and the plasma and cardiac MDA levels were significantly decreased after astaxanthin intervention in SAMP10 mice，SOD activity significantly increased， and LC3 and Beclin-1 protein expression in myocardial tissue were significantly increased（all P<0.05），and the effect of high dose was the most obvious. Compared with the medium-dose astaxanthin group，the degree of cardiac fibrosis in the medium-dose astaxanthin intervention plus 3-MA inhibitor group was increased，MDA levels in plasma and heart tissue were increased，SOD activity was decreased，LC3 and Beclin-1 protein expression in heart tissue were decreased（F=18.75， 6.353，15.77，14.08，22.83，8.657，all P<0.05）. Conclusion： Astaxanthin can improve cardiac tissue damage in SAMP10 aging mice by enhancing autophagy and reducing oxidative stress.

参考文献/References:

[1] MESCHIARI C A，ERO O K，PAN H，et al. The impact of aging on cardiac extracellular matrix[J]. Geroscience，2017，39（1）：7-18.
[2] SALCAN S，BONGARDT S，MONTEIRO BARBOSA D，et al. Elastic titin properties and protein quality control in the aging heart[J]. Biochim Biophys Acta Mol Cell Res，2020，1867（3）：118532.
[3] PICCA A，MANKOWSKI R T，BURMAN J L，et al. Mitochondrial quality control mechanisms as molecular targets in cardiac ageing[J]. Nat Rev Cardiol，2018，15（9）：543-554.
[4] KIM S H，KIM H. Inhibitory effect of astaxanthin on oxidative stress-induced mitochondrial dysfunction-A mini-review[J]. Nutrients，2018，10（9）：1137.
[5] EREN B，TUNCAY TANR■VERDI S，AYD■N K?魻SE F，et al. Antioxidant properties evaluation of topical astaxanthin formulations as anti-aging products[J]. J Cosmet Dermatol，2019，18（1）：242-250.
[6] FARRUGGIA C，KIM M B，BAE M，et al. Astaxanthin exerts anti-inflammatory and antioxidant effects in macrophages in NRF2-dependent and independent manners[J]. J Nutr Biochem，2018，62：202-209.
[7] SHAO Y，NI Y，YANG J，et al. Astaxanthin inhibits proliferation and induces apoptosis and cell cycle arrest of Mice H22 hepatoma cells[J]. Med Sci Monit，2016，22：2152-2160.
[8] SHATOOR A S，AL HUMAYED S. Astaxanthin ameliorates high-fat diet-induced cardiac damage and fibrosis by upregulating and activating SIRT1[J]. Saudi J Biol Sci，2021，28（12）：7012-7021.
[9] KIM S H，KIM H. Astaxanthin modulation of signaling pathways that regulate autophagy[J]. Mar Drugs，2019，17（10）：546.
[10] WU M X，WANG S H，XIE Y，et al. Interleukin-33 alleviates diabetic cardiomyopathy through regulation of endoplasmic reticulum stress and autophagy via insulin-like growth factor-binding protein 3[J]. J Cell Physiol. 2021，236（6）：4403-4419.
[11] SUN X，MENG H，XIAO J，et al. Pretreatment of 3-MA prevents doxorubicin-induced cardiotoxicity through inhibition of autophagy initiation[J]. Toxicology，2023，490：153512.
[12] TANEIKE M，YAMAGUCHI O，NAKAI A，et al. Inhibition of autophagy in the heart induces age-related cardiomyopathy[J]. Auto-phagy，2010，6（5）：600-606.
[13] MORI M，HIGUCHI K. The senescence-accelerated mouse as a model for geriatrics and aging biology[J]. Nihon Yakurigaku Zasshi，2019，153（4）：179-185.
[14] LIU Y，SHOJI-KAWATA S，SUMPTER R M Jr，et al. Autosis is a Na+，K+-ATPase-regulated form of cell death triggered by auto-phagy-inducing peptides，starvation，and hypoxia-ischemia[J]. Proc Natl Acad Sci U S A，2013，110（51）：20364-20371.
[15] OBAS V，VASAN R S. The aging heart[J]. Clin Sci （Lond），2018， 132（13）：1367-1382.
[16] EISENBERG T，ABDELLATIF M，SCHROEDER S，et al. Cardioprotection and lifespan extension by the natural polyamine spermidine[J]. Nat Med，2016，22（12）：1428-1438.
[17] SHI B，MA M，ZHENG Y，et al. mTOR and Beclin1：two key autophagy-related molecules and their roles in myocardial ischemia/reperfusion injury[J]. J Cell Physiol，2019，234（8）：12562-12568.
[18] VENKATARAMAN K，KHURANA S，TAI T C. Oxidative stress in aging--matters of the heart and mind[J]. Int J Mol Sci，2013，14（9）：17897-17925.
[19] SHAH A K，BHULLAR S K，ELIMBAN V，et al. Oxidative stress as a mechanism for functional alterations in cardiac hypertrophy and heart failure[J]. Antioxidants Basel，2021，10（6）：931.
[20] QU X，ZHANG Z，HU W，et al. Attenuation of the Na/K-ATPase/Src/ROS amplification signaling pathway by astaxanthin ameliorates myocardial cell oxidative stress injury[J]. Mol Med Rep，2020，22（6）：5125-5134.
[21] CUI G，LI L，XU W，et al. Astaxanthin protects ochratoxin a-induced oxidative stress and apoptosis in the heart via the Nrf2 pathway[J]. Oxid Med Cell Longev，2020，2020：7639109.
[22] YAZAKI K，YOSHIKOSHI C，OSHIRO S，et al. Supplemental cellular protection by a carotenoid extends lifespan via Ins/IGF-1 signaling in caenorhabditis elegans[J]. Oxid Med Cell Longev，2011， 2011：596240.
[23] WONG S Q，KUMAR A V，MILLS J，et al. Autophagy in aging and longevity[J]. Hum Genet，2020，139（3）：277-290.

相似文献/References:

备注/Memo

备注/Memo:

基金项目 汤臣倍健营养科学研究基金（TY0181104）
作者简介 靳可青（1999-），女，硕士在读，研究方向：营养与衰老；通信作者：张绪梅，E-mail：zhangxumei@tmu.edu.cn。

常用功能

更新日期/Last Update: 2024-01-01