title: Triptolide Attenuates Myocardial Ischemia/Reperfusion Injuries in Rats by Inducing the Activation of Nrf2/HO-1 Defense Pathway.
abstract: Triptolide is a bioactive component of Chinese herbal plant Tripterygium wilfordii Hook F that has recently been noted to attenuate hepatic and cerebral ischemia/reperfusion (I/R) injuries in rodents. To investigate whether triptolide could protect against myocardial I/R injuries, triptolide (25, 50 or 100 μg/kg) was administrated in Wistar rats that underwent left anterior descending coronary artery ligation in this study. Our data showed that triptolide pretreatment could attenuate myocardial infarction, increase the fractional shortening and left ventricular systolic pressure and decrease the left ventricular end-diastolic pressure in ischemic rats. Also, triptolide was noted to inhibit the activities of lactate dehydrogenase and creatine kinase in I/R rats. Moreover, triptolide administration suppressed macrophage infiltration, inhibited the overproduction of tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and malondialdehyde (MDA) in reperfused myocardium tissues and upregulated the activities of antioxidative superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GPx). In addition, nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the activity of its downstream target Heme oxygenase-1 (HO-1) in ischemic myocardium tissues were enhanced by triptolide pretreatment. In addition, the HO-1 inhibitor, zinc protoporphyrin-IX, abrograted the cardiac protection mediated by triptolide. Our study reveals a novel cardioprotective effect of triptolide in rats with I/R injuries, wherein the activation of Nrf2/HO-1 signaling was involved.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, People's Republic of China.
authors.forename: Haijie
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, People's Republic of China.
authors.forename: Liye
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, People's Republic of China.
authors.forename: Shijie
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, People's Republic of China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, People's Republic of China.
authors.forename: Yingxian
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, People's Republic of China. gx_qi018@163.com.|Department of Geriatrics, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, People's Republic of China. gx_qi018@163.com.
authors.forename: Guoxian
authors.initials: G
authors.lastname: Qi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004852:Epoxy Compounds / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010616:Phenanthrenes / Q000494:pharmacology*; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D002316:Cardiotonic Agents; D016207:Cytokines; D004224:Diterpenes; D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D018836:Inflammation Mediators; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D010616:Phenanthrenes; C001899:triptolide; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat
keywords: Inflammation; Myocardial ischemia/reperfusion injury; Nrf2/HO-1 signaling; Oxidative stress; Triptolide