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二十二碳六烯酸可抑制急性乙醇诱导的肝脂肪变性,其机制与下调硬脂酰辅酶 A 去饱和酶 1 和炎症细胞因子有关。

Suppression of acute ethanol-induced hepatic steatosis by docosahexaenoic acid is associated with downregulation of stearoyl-CoA desaturase 1 and inflammatory cytokines.

机构信息

Laboratory for Lipid Medicine and Technology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.

出版信息

Prostaglandins Leukot Essent Fatty Acids. 2013 May;88(5):347-53. doi: 10.1016/j.plefa.2013.02.002. Epub 2013 Mar 7.

DOI:10.1016/j.plefa.2013.02.002
PMID:23474173
Abstract

Excessive alcohol consumption can lead to hepatic steatosis. Omega-3 (n-3) polyunsaturated fatty acids (PUFA) have been shown to be effective in reducing hepatic accumulation of triglycerides (TG) by downregulation of TG biosynthesis in the liver. The aim of this study was to examine whether supplementation with the n-3 PUFA, docosahexaenoic acid (DHA), can effectively reduce acute alcohol-induced hepatic steatosis. Acute alcohol-induced hepatic steatosis was generated in 9-week-old male mice (C57BL/6J) by oral gavage of ethanol (4.7 g/kg BW) diluted in water (60%, v/v), with or without DHA (250 mg/kg BW), every 12 h for 3 administrations. Compared to the control (ethanol-alone) group, animals supplemented with DHA were protected against ethanol-induced TG accumulation in the liver. Accordingly, hepatic stearoyl-CoA desaturase-1 (SCD-1) expression, serum alanine aminotransferase (ALT) activity, and the levels of inflammatory cytokines (such as IL-6 and TNF-α) in the liver were significantly reduced, whereas the expression of heme oxygenase-1 (HO-1), an enzyme that can improve cell survival in liver tissue, was markedly increased in DHA-supplemented mice compared to the control animals. There were no differences in serum TG level and hepatic production of reactive oxygen species (ROS) between the two groups. Our findings demonstrate that DHA supplementation protects against acute ethanol-induced hepatic steatosis, which may be associated with reduced expression of SCD-1 and inflammatory cytokines.

摘要

过量饮酒可导致肝脂肪变性。已经证明,ω-3(n-3)多不饱和脂肪酸(PUFA)通过下调肝脏中甘油三酯(TG)的生物合成,有效减少肝脏中 TG 的积累。本研究旨在研究 n-3 PUFA,二十二碳六烯酸(DHA)的补充是否能有效减轻急性酒精引起的肝脂肪变性。通过用乙醇(4.7g/kgBW)在水中(60%,v/v)稀释的口服灌胃,在 9 周龄雄性小鼠(C57BL/6J)中产生急性酒精性肝脂肪变性,每 12 小时给予一次,共 3 次,同时给予或不给予 DHA(250mg/kgBW)。与对照组(仅乙醇)相比,补充 DHA 的动物可防止乙醇引起的肝 TG 积累。因此,肝硬脂酰辅酶 A 去饱和酶-1(SCD-1)的表达、血清丙氨酸转氨酶(ALT)活性以及肝内炎症细胞因子(如 IL-6 和 TNF-α)的水平显著降低,而血红素加氧酶-1(HO-1)的表达,一种可以改善肝组织中细胞存活的酶,在补充 DHA 的小鼠中明显高于对照组。两组之间血清 TG 水平和肝内活性氧(ROS)的产生没有差异。我们的研究结果表明,DHA 补充可预防急性乙醇引起的肝脂肪变性,这可能与 SCD-1 和炎症细胞因子表达减少有关。

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