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作 者:李晶[1] 李旎[1] 王剑[2] 曹衡玉[3] 陈剑超[3]
机构地区:[1]南华大学附属第二医院急诊内科,衡阳421001 [2]南华大学附属第一医院急诊科,衡阳421001 [3]南华大学附属第二医院超声医学科,衡阳421001
出 处:《基因组学与应用生物学》2017年第7期2693-2699,共7页Genomics and Applied Biology
基 金:湖南省卫生计生委科研基金(B2016136);湖南省分子靶标新药研究协同创新中心资助项目(湘教通2015351)共同资助
摘 要:氧化应激是酒精性肝病(ALD)发生的主要机制,因此具有抗氧化作用的活性物质对ALD具有潜在的治疗意义。在本研究当中,我们探讨了S-腺苷甲硫氨酸(SAM)和(或)穿心莲内酯(AD)对乙醇诱导肝细胞氧化应激损伤的保护作用。首先我们体外培养肝细胞L-02,用100 mmol/L乙醇作用24 h后发现,细胞的活性明显降低,胞内活性氧(ROS)含量显著增多以及脂质蓄积,同时细胞释放多种与肝病相关酶类如甘油三脂、胆固醇、转氨酶以及同型半胱氨酸等物质。而乙醇刺激前采用100μmol/L SAM或(和)30μmol/L AD处理细胞后,可明显降低细胞的氧化应激水平,同时能减少上述肝病相关标志物的的释放。此外,乙醇处理也可降低细胞内去乙酰化酶SIRT1的表达并抑制其核转位,而采用SAM或(和)AD处理后可进一步改善SIRT1的表达及活性。以上结果表明SAM或(和)AD能降低乙醇所致的氧化应激水平,两者联合应用可能对ALD具有潜在的治疗效果。Oxidative stress is the main mechanism of alcoholic liver disease (ALD), thus the active substance with antioxidant activity has potential therapeutic significance for ALD. In the present work, we investigated the protective effect of S-adenosylmethionine (SAM) and Andrographolide (AD) on ethanol-induced oxidative stress in hepatic cells. First, we cultured hepatic cells L-02 in vitro. Then, we exposed them to 100 mmol/L ethanol for 24 h, after which we found that the activity of the cells was decreased, the content of intracellular reactive oxygen species (ROS) increased significantly, and the lipid accumulated. At the same time, the cells released a variety of enzymes related to liver diseases, such as glycerol three fat, cholesterol, transaminase and homocysteine. On the other hand, 100 μmol/L SAM or 30 μmol/L AD treatment on cells before the stimulation of ethanol could significantly reduce the level of oxidative stress in cells and reduce the release of markers related to liver disease. Besides, ethanol treatment could also decrease the expression of SIRT1 and inhibit its nuclear translocation, but SAM or AD treatment could further improve the expression and activity of SIRT1. The above results indicated thatSAM and AD could reduce the level of oxidative stress induced by ethanol, and the combination of the two might have potential therapeutic effects on ALD.
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