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EETs mediate cardioprotection of salvianolic acids through MAPK signaling pathway

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单位: [1]Chinese Acad Med Sci, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R China [2]Peking Union Med Coll, Beijing 100050, Peoples R China [3]Chinese Acad Med Sci, Inst Mat Med, Beijing Key Lab Drug Target Identificat & Drug Sc, Beijing 100050, Peoples R China [4]China Japan Friendship Hosp, Inst Clin Med Sci, Dept Pharmacol, Beijing 100029, Peoples R China
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关键词: Salvianolic acids Acute myocardial infarction EETs/sEH MAPK

摘要:
Salvianolic acids, including salvianolic acid A (SAA) and salvianolic acid B (SAB), are the main water-soluble bioactive compounds isolated from the Chinese medicinal herb Danshen and have been shown to exert in vitro and in vivo cardiovascular protection. Recent studies suggest that epoxyeicosatrienoic acids (EETs), the primary cytochrome P450 2J (CYP2J) epoxygenase metabolites of arachidonic acid, are involved in the progression of ischemic injury in diverse organs. Here, we investigated the relation between the protective effects of salvianolic acids and EETs/sEH as well as MAPK signaling pathway. In the present study, the rat acute myocardial infarction (AMI) model was established by the left anterior descending coronary artery occlusion. Our results showed that salvianolic acids significantly reduced ST-segment elevation and serum levels of CK-MB, LDH, and ALT in AMI rats, and significantly attenuated the caspase 3 expression and reduced the ratio of Bax/Bcl-2. ELISA measurement showed that salvianolic acids significantly increased the 14,15-EET levels in blood and heart, and attenuated hydrolase activity of sEH in heart of AMI rat. Western blotting analysis suggested that salvianolic acids significantly attenuated the phosphorylation of JNK and p38, and increased phosphorylation of ERK in heart. In conclusion, these results indicate that EETs/sEH and MAPK signaling pathways are important processes in cardioprotection of salvianolic acids. (C) 2012 Institute of Materia Medica, Chinese Academy of Medical Sciences and Chinese Pharmaceutical Association. Production and hosting by Elsevier B.V. All rights reserved.

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大类 | 1 区 医学
小类 | 1 区 药学
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出版当年[2011]版:
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Q1 PHARMACOLOGY & PHARMACY

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第一作者单位: [1]Chinese Acad Med Sci, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R China [2]Peking Union Med Coll, Beijing 100050, Peoples R China [3]Chinese Acad Med Sci, Inst Mat Med, Beijing Key Lab Drug Target Identificat & Drug Sc, Beijing 100050, Peoples R China
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通讯机构: [2]Peking Union Med Coll, Beijing 100050, Peoples R China [3]Chinese Acad Med Sci, Inst Mat Med, Beijing Key Lab Drug Target Identificat & Drug Sc, Beijing 100050, Peoples R China
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