Salvianolic acid B protects against acute ethanol-induced liver injury through SIRT1-mediated deacetylation of p53 in rats
Salvianolic acid B protects against acute ethanol-induced liver injury through SIRT1-mediated deacetylation of p53 in rats
复制标题
丹酚酸 B 通过 SIRT1 介导的 p53 去乙酰化保护大鼠免受急性乙醇诱导的肝损伤
DOI：
10.1016/j.toxlet.2014.04.011
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发表时间：
2014-07-15
影响因子：
3.5
通讯作者：
Yao, Jihong
中科院分区：
文献类型：
--
作者：
Li, Mingzhu;Lu, Yang;Yao, Jihong
丹参酸B（SalB）是从传统中药丹参中分离得到的。它具有许多生物和药物活性。本研究旨在观察SalB对大鼠急性乙醇性肝损伤的影响，并探讨SIRT 1在此过程中的作用。结果表明，SalB预处理显著降低了乙醇诱导的转氨酶活性升高，降低了肝毒性细胞因子如白细胞介素-6（IL-6）的水平，并提高了抗氧化酶的活性。此外，SalB预处理逆转了由乙醇暴露引起的NF-κ B的增加、切割的caspase-3和超大B细胞淋巴瘤（Bc 1-xL）的减少。重要的是，SalB预处理显着增加了SIRT 1的表达，这是一种依赖于NAPs的脱乙酰酶，而SIRT 1的增加伴随着乙酰基-p53表达的降低。在Hep G2细胞中，SalB预处理以时间和剂量依赖性方式增加SIRT 1表达，并且这种增加被SIRT 1的siRNA敲低所消除。此外，SIRT 1的抑制显著增加了p53的乙酰化，并阻断了Sa 1B诱导的p53乙酰化下调。总之，本研究表明SalB可以通过SIRT 1介导的p53通路的去乙酰化来减轻急性乙醇诱导的肝细胞凋亡。(C)2014爱思唯尔爱尔兰有限公司版权所有。
Salvianolic acid B (SalB) is isolated from the traditional Chinese medical herb salvia miltiorrhiza. It has many biological and pharmaceutical activities. This study aimed to investigate the effect of SalB on acute ethanol-induced hepatic injury in rats and to explore the role of SIRT1 in this process. The results showed that pretreatment with SalB significantly reduced ethanol-induced elevation in aminotransferase activities, decreased hepatotoxic cytokine levels such as Interleukin-6 (IL-6), and increased the antioxidant enzyme activity. Moreover, SalB pretreatment reversed the increase in NF-KB, cleaved caspase-3 and decrease in B-cell lymphoma-extra large (Bc1-xL) caused by ethanol exposure. Importantly, SalB pretreatment significantly increased the expression of SIRT1, a NALY-dependent deacetylase, whereas the increase in SIRT1 was accompanied by decreased acetyl-p53 expression. In Hep G2 cells, SalB 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 increased the acetylation of p53, and blocked Sa1B-induced acetylation of p53 down-regulation. Collectively, this study indicated that SalB can alleviate acute ethanol-induced hepatocyte apoptosis through SIRT1-mediated deacetylation of p53 pathway. (C) 2014 Elsevier Ireland Ltd. All rights reserved.