网站首页期刊介绍通知公告编 委 会投稿须知电子期刊广告合作联系我们
最新消息:
乌梅有机酸对缺氧/复氧心肌细胞氧化应激损伤的影响及其机制
作者:代天  杨萍  邹勇  华娟  张苏川 
单位:江汉大学附属医院/武汉市第六医院 心血管内科, 湖北 武汉 430015
关键词:乌梅有机酸 缺血再灌注 心肌细胞 氧化应激 核转录因子E2相关因子2 凋亡 
分类号:R285.5
出版年·卷·期(页码):2021·49·第一期(28-33)
摘要:

目的: 研究乌梅有机酸对缺氧/复氧(H/R)诱导心肌细胞氧化应激损伤的影响及其作用机制。方法: 将心肌细胞H9C2随机分为对照组、H/R组、H/R+不同浓度乌梅有机酸组。MTT法检测心肌细胞存活,试剂盒检测超氧化物歧化酶(SOD)活性、过氧化氢酶(CAT)活性、丙二醛(MDA)水平、天冬氨酸转氨酶(AST)水平、肌酸激酶(CK)水平、乳酸脱氢酶(LDH)水平,流式细胞术检测心肌细胞凋亡,Western blotting检测Bcl2相关X蛋白(Bax)、B细胞淋巴瘤/白血病2(Bcl2)、核转录因子E2相关因子2(Nrf2)-抗氧化反应元件(ARE)信号通路相关蛋白Nrf2、血红素加氧酶1(HO-1)和醌氧化还原酶1(NQO1)的表达。结果:与对照组相比,H/R组心肌细胞存活率、SOD活性、CAT活性显著提高,MDA水平、AST水平、CK水平和LDH水平明显降低,且细胞凋亡率、Bax蛋白表达量增加,Bcl2、Nrf2、HO-1、NQO1蛋白表达量减少,差异均有统计学意义(P<0.05)。与H/R组比较,H/R+1、2 mg·ml-1乌梅有机酸组H/R损伤心肌细胞的存活率明显提高(均P<0.05);H/R损伤心肌细胞的SOD活性、CAT活性显著增加,MDA水平、AST水平、CK水平和LDH水平降低,以及心肌细胞凋亡率、Bax蛋白表达量减少,Bcl2、Nrf2、HO-1、NQO1蛋白水平提高,差异均有统计学意义(P<0.05)。结论: 乌梅有机酸可能通过激活Nrf2-ARE信号通路保护H/R导致的心肌细胞氧化应激损伤。

Objective: To study the effect of organic acid from Fructus mume on oxidative stress injury induced by hypoxia/reoxygenation (H/R) in cardiomyocytes and its mechanism.Methods: Myocardial cells H9C2 were randomly divided into control group, H/R group, H/R+group of different concentrations of organic acid. Myocardial cell survival was detected by MTT assay. Superoxide dismutase(SOD) activity, catalase(CAT) activity, malondialdehyde(MDA) content, aspartate aminotransferase(AST) level, creatine kinase(CK) level and lactate dehydrogenase(LDH) level were determined by kit. Apoptosis of cardiomyocytes was detected by flow cytometry. The expressions of Bax, Bcl2 and Nrf2-ARE signaling pathway-related proteins Nrf2, HO-1 and NQO1 were analyzed by Western blotting. Results: Compared with the control group, H/R treatment significantly reduced myocardial cell survival rate, SOD activity, CAT activity, obviously improved MDA content, AST, CK and LDH levels, and increased apoptosis rate and Bax protein expression, as well as reduced the expression of Bcl2, Nrf2, HO-1, NQO1 protein, and the differences were all significant (P<0.05). Compared with H/R group, 1, 2 mg·ml-1organic acid from Fructus mumesignificantly increased the survival rate of H/R injured cardiomyocytes (P<0.05). Compared with H/R group, organic acid from Fructus mume significantly increased SOD activity and CAT activity of H/R injured cardiomyocytes, decreased MDA content, AST, CK and LDH levels, myocardial apoptosis rate and Bax protein expression, increased Bcl2, Nrf2, HO-1, NQO1 protein levels, and the differences were all significant (P<0.05).Conclusion: Organic acid from Fructus mume protects oxidative stress damage induced by H/R by activating Nrf2-ARE signaling pathway.

参考文献:

[1] DU Y,WANG M,LIU X,et al.Araloside C prevents hypoxia/reoxygenation-induced endoplasmic reticulum stress via increasing heat shock protein 90 in h9c2 cardiomyocytes[J].Front Pharmacol,2018,9:180-193.
[2] HAUSENLOY D J,YELLON D M.Myocardial ischemia-reperfusion injury:a neglected therapeutic target[J].J Clin Invest,2013,123(1):92-100.
[3] LI Q,XIANG Y,CHEN Y,et al.Ginsenoside Rg1 protects cardiomyocytes against hypoxia/reoxygenation injury via activation of Nrf2/HO-1 signaling and inhibition of JNK[J].Cell Physiol Biochem,2017,44(1):21-37.
[4] 梁丽梅,黄照河.心肌缺血再灌注损伤发生机制及防治的研究进展[J].右江医学,2017,45(3):365-368.
[5] 国家药典委员会.中华人民共和国药典[S].北京:中国医药科技出版社,2015:79.
[6] 邓婉婷,管淑玉,李瑶,等.乌梅总有机酸的提取优化工艺及其抗氧化活性研究[J].广东药学院学报,2015,31(2):171-175.
[7] 张丹丹,姜修婷.乌梅有机酸的提取工艺及其抑菌活性[J].生物加工过程,2018,16(3):47-52.
[8] 李斌,谷松.乌梅丸及其拆方对溃疡性结肠炎大鼠结肠黏膜组织SOD与MDA影响[J].辽宁中医药大学学报,2015,17(5):48-50.
[9] 王策,扈有芹.扈有芹运用乌梅丸治疗冠心病经验[J].江西中医药,2019,50(6):28-30.
[10] 刘签兴,李晓洁.李士懋应用乌梅丸治疗心系疾病经验初探[J].环球中医药,2018,11(6):126-127.
[11] 杨文捷.基于Nrf2-ARE信号途径探讨DJ-1抗心肌细胞缺氧/复氧所诱发氧化应激损伤的分子机制[D].南昌:南昌大学,2016.
[12] 蒋有琴,刘剑,张冬颖.京尼平对缺氧/复氧心肌细胞氧化应激损伤的影响[J].中国药学杂志,2016,51(1):28-34.
[13] 柳磊,张武,李召彬,等.二氨基庚二酸激活NOD1信号通路对心肌缺血再灌注损伤的影响[J].东南大学学报(医学版),2018,37(4):691-696.
[14] GUO Y,ZHANG L,LI F,et al.Restoration of sirt1 function by pterostilbene attenuates hypoxia-reoxygenation injury in cardiomyocytes[J].Eur J Pharmacol,2016,776:26-33.
[15] 张华月,李琦,付晓伶.乌梅化学成分及药理作用研究进展[J].上海中医药杂志,2017,5(S1):296-300.
[16] JEON W K,MA J,CHOI B R,et al.Effects of fructus mume extract on MAPK and NF-κB signaling and the resultant improvement in the cognitive deficits induced by chronic cerebral hypoperfusion[J].Evid Based Complement Alternat Med,2012,2012:450838-450850.
[17] KIM M S,BANG J H,LEE J,et al.Fructus mume ethanol extract prevents inflammation and normalizes the septohippocampal cholinergic system in a rat model of chronic cerebral hypoperfusion[J].J Med Food,2016,19(2):196-204.
[18] DING S K,WANG L X,GUO L S,et al.Syringic acid inhibits apoptosis pathways via downregulation of p38MAPK and JNK signaling pathways in H9c2 cardiomyocytes following hypoxia/reoxygenation injury[J].Mol Med Rep,2017,16(2):2290-2294.
[19] NEIL GRANGER D,KVIETYS P R.Reperfusion injury and reactive oxygen species:the evolution of a concept[J].Redox Biol,2015,6:524-551.
[20] LI T,CHEN L,YU Y,et al.Resveratrol alleviates hypoxia/reoxygenation injury-induced mitochondrial oxidative stress in cardiomyocytes[J].Mol Med Rep,2019,19(4):2774-2780.
[21] LIU Z Y,HU S P,JI Q R,et al.Sevoflurane pretreatment inhibits the myocardial apoptosis caused by hypoxia reoxygenation through AMPK pathway:an experimental study[J].Asian Pac J Trop Med,2017,10(2):148-151.
[22] SHU Z,YANG Y,YANG L,et al.Cardioprotective effects of dihydroquercetin against ischemia reperfusion injury by inhibiting oxidative stress and endoplasmic reticulum stress-induced apoptosis via the PI3K/Akt pathway[J].Food Funct,2019,10(1):203-215.
[23] 蔡盈盈,陈平圣.干预肝细胞氧化应激感受器Keap1对肝星状细胞基质金属蛋白酶-2表达及其活性调节的影响[J].东南大学学报(医学版),2019,38(6):947-953.
[24] JARAMILLO M C,ZHANG D D.The emerging role of the Nrf2-Keap1 signaling pathway in cancer[J].Genes Dev,2013,27(20):2179-2191.
[25] SINGH N,AHMAD Z,BAID N,et al.Host heme oxygenase-1:friend or foe in tackling pathogens?[J].IUBMB Life,2018,70(9):869-880.
[26] LU M C,JI J A,JIANG Z Y,et al.The Keap1-Nrf2-ARE pathway as a potential preventive and therapeutic target:an update[J].Med Res Rev,2016,36(5):924-963.
[27] XUE M,MOMIJI H,RABBANI N,et al.Frequency modulated translocational oscillations of Nrf2 mediate the antioxidant response element cytoprotective transcriptional response[J].Antioxid Redox Signal,2015,23(7):613-629.
[28] ZHU Y,ZHANG Y J,LIU W W,et al.Salidroside suppresses HUVECs cell injury induced by oxidative stress through activating the Nrf2 signaling pathway[J].Molecules,2016,21(8):1033-1047.

服务与反馈:
文章下载】【发表评论】【查看评论】【加入收藏
提示:您还未登录,请登录!点此登录
您是第 744943 位访问者


 ©《现代医学》编辑部
联系电话:025-83272481;83272479
电子邮件: xdyx@pub.seu.edu.cn

苏ICP备09058541