Protective effect of linarin against D-galactosamine and lipopolysaccharide-induced fulminant hepatic failure
Protective effect of linarin against D-galactosamine and lipopolysaccharide-induced fulminant hepatic failure
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DOI：
10.1016/j.ejphar.2014.05.024
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发表时间：
2014-09-05
影响因子：
5
通讯作者：
Lee, Sun-Mee
中科院分区：
文献类型：
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作者：
Kim, Seok-Joo;Cho, Hong-Ik;Lee, Sun-Mee
莲心素是从野菊花中分离得到的。暴发性肝功能衰竭是一种严重的临床综合征，可导致大量炎症和肝细胞死亡。细胞凋亡是D-氨基半乳糖(GalN)/脂多糖(LPS)诱导的肝损伤的重要细胞病理过程，调节肝细胞凋亡可能是治疗暴发性肝衰竭的有效方法。本研究探讨了莱茵素对GalN/内毒素诱导的肝衰竭的细胞保护作用机制。小鼠在灌胃GalN(800 mg/kg)/脂多糖(40µg/kg)前1h灌胃给予Linarin(12.5、25和50 mg/kg)。利奈素可逆转GalN/脂多糖诱导的小鼠死亡。注射GalN/LPS 6h后，血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、肿瘤坏死因子-α、白介素6和干扰素-γ水平显著升高。GalN/脂多糖可增加R4和IL-1受体相关蛋白的表达。这些增加可被利巴林减弱。利奈素可减轻GalN/LPS诱导的Fas相关死亡结构域和caspase-8的表达增加，减少GalN/LPS诱导的细胞色素c和caspase-3的裂解，并减少GalN/LPS诱导的促凋亡的Bim磷酸化。但能提高抗细胞凋亡的Bclxl水平和STAT3的磷酸化水平。我们的结果提示，马钱子素通过抑制肿瘤坏死因子-α介导的细胞凋亡途径，减轻GalN/内毒素诱导的肝损伤。(C)2014年爱思唯尔。版权所有。
Linarin was isolated from Chrysanthemum indicum L. Fulminant hepatic failure is a serious clinical syndrome that results in massive inflammation and hepatocyte death. Apoptosis is an important cellular pathological process in D-galactosamine (GalN)/lipopolysaccharide (LPS)-induced liver injury, and regulation of liver apoptosis might be an effective therapeutic method for fulminant hepatic failure. This study examined the cytoprotective mechanisms of linarin against GalN/LPS-induced hepatic failure. Mice were given an oral administration of linarin (12.5, 25 and 50 mg/kg) 1 h before receiving GalN (800 mg/kg)/LPS (40 mu g/kg). Linarin treatment reversed the lethality induced by GalN/LPS. After 6 h of GalN/LPS injection, the serum levels of alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor (TNF)-alpha, interleukin-6 and interferon-gamma were significantly elevated. GalN/LPS increased roll like receptor 4 and interleukin-1 receptor associated kinase protein expression. These increases were attenuated by linarin. Linarin attenuated the increased expression of Fas-associated death domain and caspase-8 induced by GalN/LPS, reduced the cytosolic release of cytochrome c and caspase-3 cleavage induced by GalN/LPS, and reduced the pro-apoptotic Bim phosphorylation induced by GalN/LPS. However, linarin increased the level of anti-apoptotic Bcl-xL and phosphorylation of STAT3. Our results suggest that linarin alleviates GalN/LPS-induced liver injury by suppressing TNF-alpha-mediated apoptotic pathways. (C) 2014 Elsevier BY. All rights reserved.