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首页> 外文期刊>Journal of cardiovascular pharmacology and therapeutics >Cardioprotective and Anti-Aggregatory Effects of Levosimendan on Isoproterenol-Induced Myocardial Injury in High-Fat-Fed Rats Involves Modulation of PI3K/Akt/mTOR Signaling Pathway and Inhibition of Apoptosis: Comparison to Cilostazol
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Cardioprotective and Anti-Aggregatory Effects of Levosimendan on Isoproterenol-Induced Myocardial Injury in High-Fat-Fed Rats Involves Modulation of PI3K/Akt/mTOR Signaling Pathway and Inhibition of Apoptosis: Comparison to Cilostazol

机译:Levosimendan对异丙醇诱导的高脂肪喂养大鼠心肌损伤的心脏保护和抗聚合作用涉及PI3K / AKT / MTOR信号传导途径的调节和对细胞凋亡的抑制:与西洛替唑比较

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摘要

Hyperlipidemia and hypercoagulability states are linked with the increased risks of myocardial infarction (MI). Levosimendan has vasorelaxant and anti-aggregatory properties. The present study evaluated the anti-aggregatory and cardioprotective effects of levosimendan versus cilostazol in high-fat diet (HFD)-fed rats subjected to isoproterenol-induced MI. Rats were assigned to normal, HFD, HFD + isoproterenol, HFD + isoproterenol + cilostazol, and HFD + isoproterenol + levosimendan. The present study investigated the anti-aggregatory effect of both levosimendan and cilostazol and revealed that both drugs attenuated the severity of platelet aggregation. Moreover, both levosimendan and cilostazol revealed effectiveness in attenuating the severity of HFD/isoproterenol-induced myocardial injury as revealed by electrocardiogram signs, apoptotic markers, and histopathological score via counteracting the oxidative stress burden, increments in the expression of inflammatory mediators, and modulating nuclear factor kappa-B (NF-kappa B) and phosphatidylinositide 3-kinases (PI3K)/protein kinase B (Akt)/ mechanistic target of rapamycin (mTOR) pathway. It was obvious that levosimendan offered more cardioprotective properties than cilostazol. The study showed the relations between hyperlipedemia, hyperaggregability state, and myocardial injury with the modulation of NF-kappa B and PI3K/Akt/mTOR pathway.
机译:高脂血症和高凝地相同的状态与心肌梗死的风险增加(MI)。 Levosimendan具有血管链轴和抗胚胎性质。本研究评估了Levosimendan与西洛替唑在高脂肪饮食(HFD)-Fed大鼠对异丙醇诱导的MI进行的大鼠中的抗聚集和心脏保护作用。将大鼠分配给正常,HFD,HFD +异丙肾上腺素,HFD +异丙肾上腺素+西洛司唑和HFD +异丙烯醇+左旋索米酚。本研究调查了左旋索亚丹和西洛替唑的抗聚合作用,并揭示了两种药物衰减了血小板聚集的严重程度。此外,Levosimendan和西洛替唑均显示出通过抵消氧化介质的氧化胁迫负担,炎症介质表达,炎症介质的表达,并调节核因子kappa-b(Nf-κB)和磷脂酰阳性3-激酶(PI3K)/蛋白激酶B(akt)/雷帕霉素机械靶标的催化剂靶途径。很明显,Levosimendan提供比西洛塞拉酚更多的心脏保护性能。该研究表明,随着NF-Kappa B和PI3K / AKT / MTOR途径的调制,高脂血症,高可再造状态和心肌损伤之间的关系。

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