Department of Endocrinology, The First Affiliated Hospital of Xinxiang Medical University, Henan Province, China.
Department of Endocrinology, The First Affiliated Hospital of Xinxiang Medical University, Henan Province, China.
Food Chem Toxicol. 2014 Jan;63:166-73. doi: 10.1016/j.fct.2013.08.036. Epub 2013 Aug 24.
In this study, we aimed to investigate the therapeutic effects and involved mechanisms of resveratrol on an established non-alcoholic fatty liver disease (NAFLD) murine model. Wild-type and autophagic mediator ULK1 heterozygous knockout mice were induced to have NAFLD by high-fat diet for 8weeks. After that, resveratrol treatment was applied with the high-fat diet feeding for another 4weeks. Typical features of NAFLD, including histological changes, fibrosis, insulin resistance, oxidative status, and inflammation were characterized. After-treatment with resveratrol showed ameliorative effects on all measured features of NAFLD, from histology, insulin resistance, glucose tolerance to oxidative stress and inflammation. resveratrol treatment also reduced the activity of nuclear factor-κB (NF-κB) through the restoration of its inhibitor IκBα. Partial inhibition of ULK1 expression impaired the ameliorative effects of resveratrol on hepatic histology, fibrosis, oxidative status, inflammation, and NF-κB activity. In conclusion, resveratrol improved NAFLD-caused hepatic injury partially through regulating autophagic and IκBα-NF-κB pathways.
在这项研究中，我们旨在研究白藜芦醇对已建立的非酒精性脂肪性肝病（NAFLD）小鼠模型的治疗作用和相关机制。通过高脂肪饮食诱导野生型和自噬介质 ULK1 杂合子敲除小鼠 8 周，使其发生 NAFLD。之后，在高脂肪饮食喂养的同时给予白藜芦醇治疗 4 周。对 NAFLD 的典型特征，包括组织学变化、纤维化、胰岛素抵抗、氧化状态和炎症进行了特征描述。白藜芦醇治疗对 NAFLD 的所有测量特征均显示出改善作用，从组织学、胰岛素抵抗、葡萄糖耐量到氧化应激和炎症。白藜芦醇治疗还通过恢复其抑制剂 IκBα 来降低核因子-κB（NF-κB）的活性。ULK1 表达的部分抑制削弱了白藜芦醇对肝组织学、纤维化、氧化状态、炎症和 NF-κB 活性的改善作用。总之，白藜芦醇通过调节自噬和 IκBα-NF-κB 途径部分改善了 NAFLD 引起的肝损伤。
