Salvianolic acid A preconditioning confers protection against concanavalin A-induced liver injury through SIRT1-mediated repression of p66shc in mice
Salvianolic acid A preconditioning confers protection against concanavalin A-induced liver injury through SIRT1-mediated repression of p66shc in mice
复制标题
丹酚酸 A 预处理可通过 SIRT1 介导的 p66shc 抑制来预防伴刀豆球蛋白 A 诱导的小鼠肝损伤
DOI：
10.1016/j.taap.2013.08.021
复制
发表时间：
2013-11-15
影响因子：
3.8
通讯作者：
Yao, Jihong
中科院分区：
文献类型：
--
作者：
Xu, Xiaomei;Hu, Yan;Yao, Jihong
丹酚酸A （Salvianolic acid A, SalA）是从丹参中提取的酚类羧酸衍生物。它具有许多生物和药物活性。本研究旨在探讨SalA对ConA诱导的昆明小鼠急性肝损伤的影响，并探讨SIRT1在该作用中的作用。结果表明，体内预处理SalA可显著降低cona诱导的血清谷丙转氨酶（ALT）和天冬氨酸转氨酶（AST）活性升高，降低肝毒性细胞因子干扰素- γ (ifn - γ)和肿瘤坏死因子- α (tnf - α)水平。此外，SalA预处理改善了ConA暴露引起的NF-kappa B和cleaved caspase-3的升高。然而，预处理完全逆转了超大型b细胞淋巴瘤（Bcl-xL）的表达。更重要的是，SalA预处理显著增加了SIRT1的表达，SIRT1是一种NAD（+）依赖的去乙酰化酶，已知可减轻急性缺氧损伤和代谢性肝脏疾病。在我们的研究中，SIRT1的增加与生长因子适配器Shc的p66亚型（p66shc）在蛋白质和mRNA水平上的下调密切相关。在HepG2细胞培养中，SalA预处理以时间和剂量依赖的方式增加SIRT1的表达，这种增加被SIRT1的siRNA敲低所消除。此外，SIRT1抑制显著逆转p66shc的表达下降，并减弱sala诱导的p66shc下调。综上所述，本研究表明SalA可能是SIRT的有效激活剂，SalA可以通过sirt1介导的p66shc通路抑制来缓解cona诱导的肝炎。(C) 2013爱思唯尔公司版权所有。
Salvianolic acid A (SalA) is a phenolic carboxylic acid derivative extracted from Salvia miltiorrhiza. It has many biological and pharmaceutical activities. The purpose of this study was to investigate the effect of SalA on concanavalin A (ConA)-induced acute hepatic injury in Kunming mice and to explore the role of SIRT1 in such an effect. The results showed that in vivo pretreatment with SalA significantly reduced ConA-induced elevation in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and decreased levels of the hepatotoxic cytokines such as interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). Moreover, the SalA pretreatment ameliorated the increases in NF-kappa B and in cleaved caspase-3 caused by ConA exposure. Whereas, the pretreatment completely reversed expression of the B-cell lymphoma-extra large (Bcl-xL). More importantly, the SalA pretreatment significantly increased the expression of SIRT1, a NAD(+)-dependent deacetylase, which was known to attenuate acute hypoxia damage and metabolic liver diseases. In our study, the increase in SIRT1 was closely associated with down-regulation of the p66 isoform (p66shc) of growth factor adapter Shc at both protein and mRNA levels. In HepG2 cell culture, SalA pretreatment increased SIRT1 expression in a time and dose-dependent manner and such an increase was abrogated by siRNA knockdown of SIRT1. Additionally, inhibition of SIRT1 significantly reversed the decreased expression of p66shc, and attenuated SalA-induced p66shc down-regulation. Collectively, the present study indicated that SalA may be a potent activator of SIRT and that SalA can alleviate ConA-induced hepatitis through SIRT1-mediated repression of the p66shc pathway. (C) 2013 Elsevier Inc. All rights reserved.