标题:The protective effect of kaempferol on heart via the regulation of Nrf2, NF-κβ, and PI3K/Akt/GSK-3β signaling pathways in isoproterenol-induced heart failure in diabetic rats
作者:Zhang L.; Guo Z.; Wang Y.; Geng J.; Han S.
作者机构:[Zhang, L] Cardiology Department, Xidian Group Hospital, Xi'an, China;[ Guo, Z] Department of Cardiovascular, Gansu Provincial Hospital, Lanzhou, Chin 更多
通讯作者:Han, S(hanshuyi2017@sina.com)
通讯作者地址:[Han, S] Medical Research and Laboratory Diagnostic Center, Jinan Central Hospital Affiliated to Shandong UniversityChina;
来源:Drug Development Research
出版年:2019
DOI:10.1002/ddr.21495
关键词:apoptosis; diabetes; heart failure; inflammation; oxidative stress
摘要:This study was designed to delineate the effect of kaempferol (KF) on heart failure (HF) in diabetic rats. Streptozotocin-induced male diabetic rats received KF orally at 10 and 20 mg/kg for 42 consecutive days. In last 2 days of the experimental period, isoproterenol was subcutaneously injected at 85 mg/kg to induce HF. The hearts were processed for hemodynamic, biochemical, molecular, and histological investigations. Systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure were elevated in KF-treated HF-induced diabetic rats. Moreover, KF treatment resulted in decreased fasting blood glucose and glycosylated hemoglobin levels with increased serum insulin levels. Besides, serum cardiac injury markers like troponin-I, creatine kinase-muscle/brain, lactate dehydrogenase, and brain natriuretic peptide levels were significantly reduced in KF treatment. KF treatment has shown decrease in cardiac heme oxygenase-1, nuclear factor erythroid 2–related factor 2 (Nrf-2), and γ-glutamylcysteine synthetase with increased Keap1 mRNA levels. The cardioprotection of KF was improved by inhibition of apoptosis via blocking phosphorylation of Akt/glycogen synthase kinase (GSK)-3β and p38 mitogen-activated protein-kinase/extracellular signal-regulated kinases signaling pathways in HF-induced diabetic rats. Moreover, reduced cardiac apoptosis in KF treatment was confirmed by decreased terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) positive cells, histopathological changes in HF-induced diabetic rats. Therefore, the cardioprotective effect of KF is attributed to the regulation of Nrf2, nuclear factor kappa-light-chain-enhancer of activated B cells, and Akt/GSK-3β signaling pathways in HF-induced diabetic rats. © 2019 Wiley Periodicals, Inc.
收录类别:SCOPUS
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85062983349&doi=10.1002%2fddr.21495&partnerID=40&md5=bedc6e48056250ff7c02e494ba4b59d9
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