Carnosic acid alleviates chronic alcoholic liver injury by regulating the SIRT1/ChREBP and SIRT1/p66shc pathways in rats
Carnosic acid alleviates chronic alcoholic liver injury by regulating the SIRT1/ChREBP and SIRT1/p66shc pathways in rats
复制标题
鼠尾草酸通过调节 SIRT1/ChREBP 和 SIRT1/p66shc 通路减轻大鼠慢性酒精性肝损伤
DOI：
10.1002/mnfr.201500878
复制
发表时间：
2016-09-01
影响因子：
5.2
通讯作者：
Yao, Jihong
中科院分区：
文献类型：
--
作者：
Gao, Lili;Shan, Wen;Yao, Jihong
范围：鼠尾草酸（CA）是从迷迭香中提取的一种有效成分，具有多种药理活性。本研究旨在探讨CA对慢性酒精性肝损伤的作用及其机制，方法和结果：用含乙醇的流质饲料喂养大鼠建立体内模型，用100 mM乙醇处理HepG 2细胞48 h建立体外模型。在酒精性肝损伤大鼠模型中，CA显著降低血清转氨酶、甘油三酯和总胆固醇水平。此外，CA抑制氧化应激、炎症和细胞死亡。有趣的是，CA激活SIRT 1，这与脂蛋白碳水化合物反应元件结合蛋白（ChREBP）和生长因子衔接蛋白（p66 shc）的下调有关。在HepG 2细胞中，乙醇诱导的细胞损伤与SIRT 1降低和ChREBP和p66 shc蛋白表达增加相关。这些变化被CA逆转，但被特异性SIRT 1抑制剂EX 527增强。结论：CA通过激活SIRT 1/ChREBP和SIRT 1/p66 shc通路对酒精性肝损伤具有保护作用，其机制可能与抗脂肪变性、抗氧化和抗凋亡有关。
Scope: Carnosic acid (CA), which is extracted from rosemary, displays multiple pharmacological activities. This study aimed to investigate the effects of CA on chronic alcoholic liver injury and to elucidate the related mechanisms.Methods and results: An in vivo ratmodel was established by feeding rats a liquid diet containing ethanol, and an in vitromodel was created by treating HepG2 cells with 100 mM ethanol for 48 h. In the ratmodel of alcohol-induced liver injury, CA significantly decreased serum aminotransferase, triglyceride and total cholesterol levels. Additionally, CA inhibited oxidative stress, inflammation, and cell death. Interestingly, CA activated SIRT1, which was associated with the downregulation of lipoprotein carbohydrate response element-binding protein (ChREBP) and growth factor adapter protein (p66shc). In HepG2 cells, ethanol-induced cell injury was associated with decreased SIRT1 and increased ChREBP and p66shc protein expression. These changes were reversed by CA but enhanced by a specific SIRT1 inhibitor, EX527. Moreover, the effects of CA on SIRT1, ChREBP, and p66shc were abolished by SIRT1 siRNA or EX527, indicating that CA decreased ChREBP and p66shc expression via SIRT1 activation.Conclusion: CA exerted protective effects against alcoholic liver injury by activating the SIRT1/ChREBP and SIRT1/p66shc pathways, which are related to the anti-steatosis, antioxidant, and anti-apoptosis effects.