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黄芪甲苷IV通过抑制氧化应激和钙蛋白酶-1激活减轻肥厚型心肌细胞的凋亡。

Astragaloside IV attenuates apoptosis of hypertrophic cardiomyocyte through inhibiting oxidative stress and calpain-1 activation.

作者信息

Mei Meng, Tang Futian, Lu Meili, He Xin, Wang Hongxin, Hou Xuwei, Hu Jin, Xu Chonghua, Han Ronghui

机构信息

Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Drug Research Institute, Liaoning Medical University, Jinzhou, Liaoning, PR China.

Internal Medicine-Cardiovascular Department, The First Affiliated Hospital of Liaoning Medical University, PR China.

出版信息

Environ Toxicol Pharmacol. 2015 Nov;40(3):764-73. doi: 10.1016/j.etap.2015.09.007. Epub 2015 Sep 16.

Abstract

Calpain-1 activation and oxidative stress are two critical factors contributing to apoptosis of hypertrophic cardiomyocyte. Astragaloside IV (ASIV) exhibits protective effect against various heart diseases. The present study was designed to investigate whether the inhibitory effect of ASIV on isoproterenol (ISO)-induced apoptosis of hypertrophic cardiomyocyte was associated with the anti-oxidation and calpain-1 inhibition. Hypertrophy, apoptosis, mitochondrial oxidative stress and calpain-1 expression were measured in the heart tissue of Sprague-Dawley (SD) rats and H9C2 cells treated with ISO alone or combination with ASIV. The results showed that ASIV attenuated apoptotic rate, increased Bcl-2 expression, decreased Bax expression, ameliorated the integrity of mitochondrial structure and improved mitochondrial membrane potential (MMP). Moreover, ASIV combination reduced both calpain-1 protein expression and calpain activity, down-regulated mitochondrial NOX4 (mito-NOX4) expression, increased activity of mitochondrial superoxide dismutase (mito-SOD) and mitochondrial catalase (mito-CAT) compared to ISO treated alone. The results suggested that ASIV exerted anti-apoptosis effect on ISO-induced hypertrophic cardiomyocyte by attenuating oxidative stress and calpain-1 activation.

摘要

钙蛋白酶-1激活和氧化应激是导致肥厚型心肌细胞凋亡的两个关键因素。黄芪甲苷(ASIV)对多种心脏病具有保护作用。本研究旨在探讨ASIV对异丙肾上腺素(ISO)诱导的肥厚型心肌细胞凋亡的抑制作用是否与抗氧化和钙蛋白酶-1抑制有关。在单独用ISO或与ASIV联合处理的Sprague-Dawley(SD)大鼠和H9C2细胞的心脏组织中测量肥大、凋亡、线粒体氧化应激和钙蛋白酶-1表达。结果表明,ASIV降低了凋亡率,增加了Bcl-2表达,降低了Bax表达,改善了线粒体结构的完整性并提高了线粒体膜电位(MMP)。此外,与单独用ISO处理相比,ASIV联合用药降低了钙蛋白酶-1蛋白表达和钙蛋白酶活性,下调了线粒体NOX4(mito-NOX4)表达,增加了线粒体超氧化物歧化酶(mito-SOD)和线粒体过氧化氢酶(mito-CAT)的活性。结果表明,ASIV通过减轻氧化应激和钙蛋白酶-1激活对ISO诱导的肥厚型心肌细胞发挥抗凋亡作用。

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