关键词: Artesunate Cardiac hypertrophy Cardioprotective NF-κB SIRT1

Mesh : Animals Artesunate / pharmacology therapeutic use Sirtuin 1 / metabolism Isoproterenol / toxicity NF-kappa B / metabolism Male Cardiomegaly / chemically induced drug therapy pathology prevention & control Rats Oxidative Stress / drug effects Artemisinins / pharmacology therapeutic use Myocytes, Cardiac / drug effects metabolism pathology Cardiotonic Agents / pharmacology therapeutic use Rats, Sprague-Dawley

来  源:   DOI:10.1016/j.ejphar.2024.176709

Abstract:
Cardiac Hypertrophy is an adaptive response of the body to physiological and pathological stimuli, which increases cardiomyocyte size, thickening of cardiac muscles and progresses to heart failure. Downregulation of SIRT1 in cardiomyocytes has been linked with the pathogenesis of cardiac hypertrophy. The present study aimed to investigate the effect of Artesunate against isoprenaline induced cardiac hypertrophy in rats via SIRT1 inhibiting NF-κB activation. Experimental cardiac hypertrophy was induced in rats by subcutaneous administration of isoprenaline (5 mg/kg) for 14 days. Artesunate was administered simultaneously for 14 days at a dose of 25 mg/kg and 50 mg/kg. Artesunate administration showed significant dose dependent attenuation in mean arterial pressure, electrocardiogram, hypertrophy index and left ventricular wall thickness compared to the disease control group. It also alleviated cardiac injury biomarkers and oxidative stress. Histological observation showed amelioration of tissue injury in the artesunate treated groups compared to the disease control group. Further, artesunate treatment increased SIRT1 expression and decreased NF-kB expression in the heart. The results of the study show the cardioprotective effect of artesunate via SIRT1 inhibiting NF-κB activation in cardiomyocytes.
摘要:
心肌肥厚是机体对生理和病理刺激的适应性反应,这增加了心肌细胞的大小,心肌增厚并进展为心力衰竭。心肌细胞中SIRT1的下调与心脏肥大的发病机理有关。本研究旨在探讨青蒿琥酯通过SIRT1抑制NF-κB活化对异丙肾上腺素诱导的大鼠心肌肥厚的影响。通过皮下施用异丙肾上腺素(5mg/kg)14天在大鼠中诱导实验性心脏肥大。青蒿琥酯以25mg/kg和50mg/kg的剂量同时给药14天。青蒿琥酯给药显示平均动脉压显著的剂量依赖性衰减,心电图,与疾病对照组相比,肥大指数和左心室壁厚度。它还减轻了心脏损伤生物标志物和氧化应激。组织学观察显示青蒿琥酯治疗组与疾病对照组相比组织损伤改善。Further,青蒿琥酯治疗可增加心脏中SIRT1的表达,并降低NF-kB的表达。研究结果表明青蒿琥酯通过SIRT1抑制心肌细胞中NF-κB活化的心脏保护作用。
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