芪冬颐心口服液激活Nrf2/HO-1信号通路减轻阿霉素诱导的小鼠心肌损伤

陈荣昌; 杨龙坡; 马晓玉; 徐丽娇; 邹敬韬; 孙桂波; 孙晓波

doi:10.13422/j.cnki.syfjx.20192442

您当前的位置：

首页 >

文章列表页 >

芪冬颐心口服液激活Nrf2/HO-1信号通路减轻阿霉素诱导的小鼠心肌损伤

药理 | 更新时间：2021-02-09

- 芪冬颐心口服液激活Nrf2/HO-1信号通路减轻阿霉素诱导的小鼠心肌损伤
- Qidong Yixin Oral Liquid Activates Nrf2/HO-1 Signaling Pathway to Alleviate Adriamycin-induced Myocardial Injury in Mice
- 中国实验方剂学杂志 2020年26卷第1期页码：65-70
- 作者机构：
  
  1.中国医学科学院　药用植物研究所，北京　 100094
  2.通化华夏药业有限责任公司，吉林通化　 134100
- 作者简介：
  
  [第一作者]　陈荣昌，博士，副研究员，从事中药药理毒理研究，E-mail：chenrongchang456@126.com
  *孙桂波，博士，研究员，从事中药药理毒理研究，E-mail：sunguibo@126.com；
  *孙晓波，博士，研究员，从事中药药理毒理研究，E-mail： sun-xiaobo@163.com
- 基金信息：
  
  吉林省科技发展计划项目(201603004YY)
- DOI：10.13422/j.cnki.syfjx.20192442
  中图分类号： R2-0; R289; R285.5; R541.4
- 收稿日期：2019-07-24，
  
  网络出版日期：2019-09-06，
  
  纸质出版日期：2020-01-05
- 稿件说明：
移动端阅览
陈荣昌, 杨龙坡, 马晓玉, 等. 芪冬颐心口服液激活Nrf2/HO-1信号通路减轻阿霉素诱导的小鼠心肌损伤[J]. 中国实验方剂学杂志, 2020,26(1):65-70.

Rong-chang CHEN, Long-po YANG, Xiao-yu MA, et al. Qidong Yixin Oral Liquid Activates Nrf2/HO-1 Signaling Pathway to Alleviate Adriamycin-induced Myocardial Injury in Mice[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(1): 65-70.
陈荣昌, 杨龙坡, 马晓玉, 等. 芪冬颐心口服液激活Nrf2/HO-1信号通路减轻阿霉素诱导的小鼠心肌损伤[J]. 中国实验方剂学杂志, 2020,26(1):65-70. DOI： 10.13422/j.cnki.syfjx.20192442.

Rong-chang CHEN, Long-po YANG, Xiao-yu MA, et al. Qidong Yixin Oral Liquid Activates Nrf2/HO-1 Signaling Pathway to Alleviate Adriamycin-induced Myocardial Injury in Mice[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(1): 65-70. DOI： 10.13422/j.cnki.syfjx.20192442.

摘要

目的：

研究芪冬颐心口服液对阿霉素(DOX)诱导的小鼠心肌毒性保护作用及机制。

方法：

90只雄性ICR小鼠随机分为正常组，模型(DOX)组，DOX＋芪冬颐心口服液组(9.55，23.88，47.75 g·kg

-1

)及芪冬颐心口服液高剂量组(47.75 g·kg

-1

)，每组15只。正常组、模型组灌胃给予纯净水，芪冬颐心口服液组各剂量组灌胃给予不同剂量的芪冬颐心口服液，每天1次，给药21 d，在第7天正常组及芪冬颐心口服液高剂量组腹腔注射生理盐水，其余各组均腹腔注射阿霉素(15 mg·kg

-1

)。21 d后小鼠称量体质量和心重，计算心脏指数；取血清用于乳酸脱氢酶(LDH)，肌酸激酶(CK)，天门冬氨酸氨基转移酶(AST)检测；取心脏用于苏木素-伊红(HE)染色；检测心肌组织内超氧化物歧化酶(SOD)，谷胱甘肽过氧化物酶(GSH-PX)，过氧化氢酶(CAT)活性，采用蛋白免疫印迹法(Western blot)检测核转录因子NF-E2相关因子(Nrf2)，血红素氧合酶-1(HO-1)的表达。

结果：

与正常组比较，阿霉素可引起小鼠体质量显著降低(

0.01)，血清LDH，CK，AST活性显著升高(

0.01)，抗氧化酶活力降低(

0.01)；与DOX组比较，芪冬颐心口服液中、高剂量预给药可以显著提高小鼠体质量(

0.05，

0.01)，降低心肌三酶水平(

0.01)，提高抗氧化酶活力(

0.05，

0.01)，提高Nrf2及HO-1表达水平(

0.01)。

结论：

芪冬颐心口服液对阿霉素心肌毒性具有很好的保护作用，其作用机制可能与激活Nrf2/HO-1信号通路，减轻氧化应激损伤有关。

Abstract

Objective:

To study the protective effect and mechanism of Qidong Yixin oral liquid on doxorubicin-induced myocardial toxicity in mice.

Method:

Ninety male ICR mice were randomly divided into normal group

model(DOX) group

DOX+ Qidong Yixin oral liquid group (9.55

23.88

47.75 g·kg

-1

) and high dose group (47.75 g·kg

-1

) with 15 mice in each group. The normal group and model group were given pure water by gavage

and each dose group of Qidong Yixin oral liquid was given different doses of Qidong Yixin oral liquid once a day for 21 days. On the seventh day

normal saline was injected into the abdominal cavity of the normal group and the high dose group of Qidong Yixin oral liquid. Doxorubicin was injected into the abdominal cavity of the other groups (15 mg·kg

-1

). After 21 days

the weight and heart weight of mice were weighed and cardiac index was calculated. Serum was taken for the detection of lactate dehydrogenase (LDH)

creatine kinase (CK)

aspartate aminotransferase (AST). Heart was taken for hematoxylin-eosin (HE) staining

superoxide dismutase (SOD)

glutathione peroxidase (GSH-PX)

catalase (CAT) in myocardial tissue were detected. The expression of nuclear factor NF-E2 related factor (Nrf2) and heme oxygenase-1 (HO-1) were detected by Western blot.

Result:

Compared with normal group

adriamycin could significantly reduce the body weight of mice (

0.01)

increase the activities of LDH

CK and AST in serum(

0.01)

and decrease the activities of antioxidant enzymes (

0.01). Compared with DOX group

high dose Qidong Yixin oral liquid could significantly increase the weight of mice (

0.05

0.01)

decrease the level of myocardial three enzymes(

0.01)

increase the activity of antioxidant enzymes(

0.05

0.01)

and increase the expression of Nrf2 and HO-1(

0.01).

Conclusion:

Qidong Yixin oral liquid has a good protective effect on doxorubicin myocardial toxicity. Its mechanism may be related to activating Nrf2/HO-1 signaling pathway and alleviating oxidative stress injury.

关键词

Keywords

references

赵刚，祁静蕙，胡增华，等．国产阿霉素相同剂量不同用药方案静脉滴注药代动力学及疗效与毒副反应的研究 [J]．中国肿瘤临床， 1992 ， 19 ( 5 )： 375 - 380 .

L Gianni ， E H Herman ， S E Lipshultz ， et al . Anthracycline cardiotoxicity: from bench to bedside [J]． J Clin Oncol ， 2008 ， 26 ( 22 )： 3777 - 3784 .

R C CHEN , X D XU , X Z LIU , et al . Total flavonoids from Clinopodium chinense (Benth.) O. Ktze protect against doxorubicin-induced cardiotoxicity in vitro and in vivo [J]. Evid Based Complement Alternat Med ， 2015 ， doi： 10.1155/2015/472565 http://dx.doi.org/10.1155/2015/472565 .

R C CHEN , G B SUN , J X YE , et al . Salvianolic acid B attenuates doxorubicin-induced ER stress by inhibiting TRPC3 and TRPC6 mediated Ca 2＋ overload in rat cardiomyocytes [J]. Toxicol Let , 2017 , 276 ： 21 - 30 .

R C CHEN ， G B SUN ， L P YANG ， et al . Salvianolic acid B protects against doxorubicin induced cardiac dysfunction via inhibition of ER stress mediated cardiomyocyte apoptosis [J]. Toxicol Res ， 2016 ， 5 ( 5 )： 1335 - 1345 .

罗敏，龙波，潘玲，等．芪冬颐心口服液联合磷酸肌酸钠对病毒性心肌炎的临床效果观察 [J]．中药药理与临床， 2017 ， 33 ( 6 )： 143 - 146 .

王冰梅，侯宜，赵一晖，等．芪冬颐心口服液对柯萨奇B3病毒感染的乳鼠心肌细胞的保护作用研究 [J]．中华中医药学刊， 2004 ， 22 ( 6 )： 1078 - 1079 .

王岩，许兵丽．芪冬颐心口服液联合曲美他嗪治疗病毒性心肌炎的临床效果观察 [J]．中国医药指南， 2016 ， 14 ( 26 )： 205 - 206 .

祁烁．芪冬颐心口服液防治化疗心脏毒性及其改善心气虚证的研究 [D]．北京：北京中医药大学， 2018 .

王瑞华，李艳芬，邹爱英，等．黄连阿胶汤防治蒽环类化疗药物诱发心肌损伤的临床疗效及机制 [J]．中国实验方剂学杂志， 2018 ， 25 ( 8 )： 20 - 27 .

高玲，粟栗，杨婷，等．强心活性力对阿霉素引起心脏毒性的保护作用 [J]．中国实验方剂学杂志， 2019 ， 24 ( 14 )： 153 - 158 .

J Ghosh , J Das , P Manna , et al . The protective role of arjunolic acid against doxorubicin induced intracellular ROS dependent JNK-p38 and p53-mediated cardiac apoptosis [J]. Biomaterials , 2011 , 32 ( 21 ): 4857 - 4866 .

G Takemura ， H Fujiwara . Doxorubicin-induced cardiomyopathy from the cardiotoxic mechanisms to management [J]. Prog Cardiovasc Dis , 2007 , 49 ( 5 ): 330 - 352 .

L Szweda , T Oberley , D S Clair , et al . Oxidative damage precedes nitrative damage in adriamycin-induced cardiac mitochondrial injury [J]. Toxicol Pathol , 2004 , 32 ( 5 ): 536 - 547 .

E Aldieri . Doxorubicin induces an increase of nitric oxide synthesis in rat cardiac cells that is inhibited by iron supplementation [J]. Toxicol Appl Pharmacol , 2002 , 185 ( 2 ): 85 - 90 .

W C F Brilhante , Z L de Aguiar , A Etges , et al . Effects of the antioxidant agent tempol on periapical lesions in rats with doxorubicin-induced cardiomyopathy [J]. J Endod , 2012 , 38 ( 2 ): 191 - 195 .

Y H CHEN , S F Yet , M A Perrella , et al . Role of heme oxygenase-1 in the regulation of blood pressure and cardiac function [J]. Exp Biol Med ， 2003 , 228 ( 5 ): 447 - 453 .

R C Siow , T Ishii , G E Mann , et al . Modulation of antioxidant gene expression by 4-hydroxynonenal: athero protective role of the Nrf2/ARE transcription pathway [J]. Redox Rep , 2007 , 12 ( 1/2 ): 11 - 15 .

R T Kolamunne , I H Dias , A B Vernallis , et al . Nrf2 activation supports cell survival during hypoxia and hypoxia/reoxygenation in cardiomyoblasts, the roles of reactive oxygen and nitrogen species [J]. Redox Biol , 2013 , 1 ( 1 ): 418 - 426 .

T Nguyen , P Nioi , C B Pickett , et al . The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress [J]. J Biol Chem , 2009 , 284 ( 20 ): 13291 - 13295 .

S Fourquet , R Guerois , D Biard , et al . Activation of NRF2 by nitrosative agents and H 2 O 2 involves Keap1 disulfide formation [J]. J Biol Chem , 2010 , 285 ( 11 ): 8463 - 8471 .

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

阳和汤血清增强阿霉素对MCF-7肿瘤细胞抑制作用机制的研究

犀角地黄汤干预PKM2介导的一碳代谢途径调控脓毒症炎症反应的机制

线粒体质量控制调控肌少症发病机制及其中医药干预的研究进展

当归芍药散加味调控JNK/p38 MAPK通路改善痤疮炎症和凋亡的机制

子宫内膜异位症程序性细胞死亡和中医药干预作用研究进展