Betulin alleviated ethanol-induced alcoholic liver injury via SIRT1/AMPK signaling pathway
Betulin alleviated ethanol-induced alcoholic liver injury via SIRT1/AMPK signaling pathway
复制标题
桦木醇通过 SIRT1/AMPK 信号通路减轻乙醇诱导的酒精性肝损伤
DOI：
10.1016/j.phrs.2015.12.022
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发表时间：
2016-03-01
影响因子：
9.3
通讯作者：
Nan, Ji-Xing
中科院分区：
文献类型：
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作者：
Bai, Ting;Yang, Yong;Nan, Ji-Xing
本研究旨在探讨白桦树皮中的三萜成分白桦醇对酒精性肝损伤的保护作用及其可能的机制。体外培养人肝星状细胞系LX-2细胞，分别用白桦醇(6.25、12.5、25mU M)和乙醇(50 MM)作用24 h，四甲基偶氮唑盐比色法检测细胞存活率，Western印迹法检测细胞蛋白表达。在体内，我们建立了雄性C57BL/6小鼠酒精性肝损伤模型，将其置于含Lieber-DeCarli乙醇的饲料中10天，然后通过灌胃给予单剂量乙醇(5g/kg体重)。白桦醇(20和50 mg/kg)每天灌胃给药。体外实验结果表明，白桦脂醇能有效降低LX-2细胞的存活率，降低I型胶原、α-SMA、活化的肝细胞激酶B-1(LKB1)和一磷酸腺苷激活的蛋白激酶(AMPK)的磷酸化水平。白桦醇可抑制乙醇处理的LX-2细胞中固醇调节元件结合蛋白-1(SREBP-1)的表达，AMPK基因缺失可阻断白桦醇对SREBP-1的影响。在体内，白桦脂醇减轻了长期酗酒小鼠血清转氨酶和甘油三酯水平的升高，同时显著抑制了SREBP-1的表达和激活了LKB1-AMPK的磷酸化。此外，白桦醇还能增强乙醇诱导的sirtuin 1(SIRT1)的表达。综上所述，白桦醇可能通过阻断SREBP-1对脂肪酸合成的调节，激活SIRT1-LKB1-AMPK信号通路，从而减轻酒精性肝损伤。(C)2015爱思唯尔有限公司。保留所有权利。
The present study was conducted to investigate the protective effect of betulin, a triterpene from the bark of Betula platyphylla Suk, against ethanol-induced alcoholic liver injury and its possible underlying mechanisms. In vitro, human hepatic stellate cell line, LX-2 cells were treated with betulin (6.25, 12.5 and 25 mu M) prior to ethanol (50 mM) for 24 h. Cell viability was analyzed by methyl thiazolyl tetrazolium assay, protein expressions were assessed by Western blot. In vivo, we induced alcoholic liver injury in male C57BL/6 mice, placing them on Lieber-DeCarli ethanol-containing diets for 10 days and then administering a single dose of ethanol (5 g/kg body weight) via gavage. Betulin (20 and 50 mg/kg) were given by gavage every day. In vitro results showed that betulin effectively decreased LX-2 cell viability, attenuated collagen-I, alpha-smooth muscle actin (alpha-SMA) levels, activated liver kinase B-1 (LKB1) and adenosine monophosphate-activated protein kinase (AMPK) phosphorylation. Betulin suppressed the expression of sterol regulatory element-binding protein-1 (SREBP-1), and genetic deletion of AMPK blocked the effect of betulin on SREBP-1 in ethanol treated LX-2 cells. In vivo, betulin attenuated the increases in serum aminotransferase and triglyceride levels in the mice fed with chronic-binge ethanol, while significantly inhibited SREBP-1 expression and activated LKB1-AMPK phosphorylation. Additionally, betulin enhanced the sirtuin 1 (SIRT1) expression mediated by ethanol. Taken together, betulin alleviates alcoholic liver injury possibly through blocking the regulation of SREBP-1 on fatty acid synthesis and activating SIRT1-LKB1-AMPK signaling pathway. (C) 2015 Elsevier Ltd. All rights reserved.