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丹酚酸 B 通过抑制 PARP-1 保护心肌细胞免受血管紧张素 II 诱导的肥大。

Salvianolic acid B protects cardiomyocytes from angiotensin II-induced hypertrophy via inhibition of PARP-1.

机构信息

Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.

School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong, China.

出版信息

Biochem Biophys Res Commun. 2014 Feb 14;444(3):346-53. doi: 10.1016/j.bbrc.2014.01.045. Epub 2014 Jan 22.

DOI:10.1016/j.bbrc.2014.01.045
PMID:24462865
Abstract

Salvianolic acid B (SalB), one of the major bioactive components in Salviamiltiorrhiza, has plenty of cardioprotective effects. The present study was designed to investigate the effect of SalB on angiotensin II (AngII)-induced hypertrophy in neonatal rat cardiomyocytes, and to find out whether or not this effect is attributed to inhibition of poly (ADP-ribose) polymerase-1 (PARP-1), which plays a key role in cardiac hypertrophy. Our results showed that SalB prevented the cardiomyocytes from AngII-induced hypertrophy, associated with attenuation of the mRNA expressions of atrial natriuretic factor and brain natriuretic peptide, and reduction in the cell surface area. SalB inhibited the activity of PARP-1. The inhibitory effect was comparable to that of the PARP-1 inhibitor 3-Aminobenzamide (3-AB). In addition, SalB reversed the depletion of cellular NAD(+) induced by AngII. Moreover, overexpression of PARP-1 attenuated the anti-hypertrophic effect of SalB. These observations suggested that SalB prevented the cardiomyocytes from AngII-induced hypertrophy, at least partially through inhibition of PARP-1. Moreover, SalB attenuated the generation of oxidative stress via suppression of NADPH oxidase 2 and 4, which might probably contribute to the inhibition of PARP-1. These present findings may shed new light on the understanding of the cardioprotective effect of SalB.

摘要

丹酚酸 B(SalB)是丹参的主要生物活性成分之一,具有丰富的心脏保护作用。本研究旨在探讨 SalB 对血管紧张素 II(AngII)诱导的新生大鼠心肌细胞肥大的影响,并确定这种作用是否归因于对多聚(ADP-核糖)聚合酶-1(PARP-1)的抑制,PARP-1 在心肌肥大中起着关键作用。我们的结果表明,SalB 可防止心肌细胞发生 AngII 诱导的肥大,同时减弱心钠肽和脑钠肽的 mRNA 表达,并减小细胞表面积。SalB 抑制 PARP-1 的活性。抑制作用与 PARP-1 抑制剂 3-氨基苯甲酰胺(3-AB)相当。此外,SalB 逆转了 AngII 诱导的细胞内 NAD+耗竭。此外,PARP-1 的过表达减弱了 SalB 的抗肥大作用。这些观察结果表明,SalB 通过抑制 PARP-1 来防止心肌细胞发生 AngII 诱导的肥大。此外,SalB 通过抑制 NADPH 氧化酶 2 和 4 来减轻氧化应激的产生,这可能有助于抑制 PARP-1。这些发现可能为理解 SalB 的心脏保护作用提供新的思路。

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