Metformin and tanshinone llA as ethnodrugs protect heart against injury by inhibiting microRNA-1

Metformin and tanshinone llA as ethnodrugs protect heart against injury by inhibiting

microRNA-1

Lei JIAO;Ying ZHANG;Xue LIU;Lu ZHANG;Hong-li SHAN;Yong ZHANG;Bao-feng YANG

【期刊名称】《中国药理学与毒理学杂志》 【年(卷),期】2018(032)004

【摘要】OBJECTIVE To explore the protection mechanism of metformin and tanshinone IIA on myocardial injury. METHODS The cultured neonatal rat ventricular cells (NRVCs) were exposed to 100 μmol·L-1H2O2to simulate the in vitro model of ischemia-reperfusion injury.MTT,TUNEL and Viability/Cytotoxicity Assay were used to evaluate the effect of metformin on the viability of cardiomyocytes after treated with H2O2. The target of miR-1 was verified by Dual luciferase reporter assay. ChIP analyses was adopted to reveal the relationship between C/EBP β and miR-1.Tanshinone IIA was administrated daily for 7 d before ligation of the left anterior descending artery (LAD) and lasted for 3 months after LAD.Whole-cell patch-clamp techniques were used to measure the inward rectifying K+current(IK1)in rat isolated ventricular myocytes.GRP94,p-AMPKα,C/EBP β,CHOP,Caspase-3,Kir2.1,p38 MAPK, Cx43, MEF2 and SRF levels were analyzed by Western blot and miR-1 level was quantified by Real-time PCR.RESULTS The expression of miR-1 was significantly increased in NRVCs exposed to H2O2 in vitro. miR-1

was shown to target the 3′-untranslated region (UTR) of GRP94, which results in the accumulation of un/misfolded proteins,leading to the endoplasmic upregulation

reticulum(ER)stress.C/EBP

of

miR-1

by

β

directly binding

induces

to

the its

promoter.Furthermore,metformin,a direct allosteric AMPK activator, significantly reduces C/EBP β and miR-1 levels comparing with control group. Similarly, tanshinone IIA decreased the incidence of arrhythmias and relieved ischemia-induced injury.Moreover, tanshinone IIA depressed the elevated miR-1 level and inhibited the activation of p38 MAPK and heart special transcription factors SRF and MEF2 in ischemic cardiomyocytes. CONCLUSION Metformin protects cardiomyocytes against

H2O2damage

through

AMPK/C/EBPβ/miR-1/GRP94

pathway.Tanshi-none IIA play a role in protection cardiomyocytes from ischemic injury based on inhibiting miR-1 expres-sion through p38 MAPK signal pathway. 【总页数】1页(290) 【关键词】

【作者】Lei JIAO;Ying ZHANG;Xue LIU;Lu ZHANG;Hong-li SHAN;Yong ZHANG;Bao-feng YANG

【作者单位】Department of Pharmacology(the State-Province Key Laboratories of Biomedicine Pharmaceutics of China Key Laboratory of Cardiovascular Research,Ministry of Education),College of Pharmacy,

Harbin Medical University,Harbin,China;Department of

Pharmacology(the State-Province Key Laboratories of Biomedicine Pharmaceutics

of

China

Key

Laboratory

of

Cardiovascular

Research,Ministry of Education),College of Pharmacy, Harbin Medical University,Harbin,China;Department

of

Pharmacology(the

State-

Province Key Laboratories of Biomedicine Pharmaceutics of China Key Laboratory of Cardiovascular Research,Ministry of Education),College of Pharmacy, Harbin Medical University,Harbin,China;Department of Pharmacology(the State-Province Key Laboratories of Biomedicine Pharmaceutics

of

China

Key

Laboratory

of

Cardiovascular

Research,Ministry of Education),College of Pharmacy, Harbin Medical University,Harbin,China;Department

of

Pharmacology(the

State-

Province Key Laboratories of Biomedicine Pharmaceutics of China Key Laboratory of Cardiovascular Research,Ministry of Education),College of Pharmacy, Harbin Medical University,Harbin,China;Department of Pharmacology(the State-Province Key Laboratories of Biomedicine Pharmaceutics

of

China

Key

Laboratory

of

Cardiovascular

Research,Ministry of Education),College of Pharmacy, Harbin Medical University,Harbin,China;Institute of Metabolic Disease,Heilongjiang Academy of Medical Science,Harbin 150081,China;Department of Pharmacology(the State-Province Key Laboratories of Biomedicine Pharmaceutics

of

China

Key

Laboratory

of

Cardiovascular

Research,Ministry of Education),College of Pharmacy, Harbin Medical University,Harbin,China;Faculty

of

Medicine,Department

of

Pharmacology and Therapeutics,Melbourne School of Biomedical Sciences,Dentistry

and

Health

Sciences,University

of

Melbourne,Melbourne,Australia 【正文语种】英文 【中图分类】 【文献来源】

https://www.zhangqiaokeyan.com/academic-journal-cn_chinese-journal-pharmacology-toxicology_thesis/0201242139166.html 【相关文献】

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