Xue Meilan, Liang Hui, Zhou Zhitong, Liu Ying, He Xinjia, Zhang Zheng, Sun Ting, Yang Jia, Qin Yimin, Qin Kunpeng
Department of Biochemistry and Molecular Biology, Basic Medical College, Qingdao University of Medicine, Qingdao, PR China.
The Institute of Human Nutrition, College of Public Health, Qingdao University of Medicine, 308# Ningxia Road, Qingdao, 266071, PR China.
Food Nutr Res. 2021 Apr 20;65. doi: 10.29219/fnr.v65.5384. eCollection 2021.
Alcoholic liver disease is caused as a result of chronic alcohol consumption. In this study, we used an alcoholic liver injury mouse model to investigate the effect of fucoidan on ethanol-induced liver injury and steatosis and the underlying mechanisms.
All mice were randomly divided into four groups: 1) control group, 2) model group, 3) diammonium glycyrrhizinate treatment group (200 mg/kg body weight), and 4) fucoidan treatment group (300 mg/kg body weight). Administration of ethanol for 8 weeks induced liver injury and steatosis in mice.
Fucoidan treatment decreased serum alanine aminotransferase activity, serum total cholesterol levels, and hepatic triglyceride levels, and improved the morphology of hepatic cells. Fucoidan treatment upregulated the expression of AMPKα1, SIRT1, and PGC-1α and inhibited the expression of ChREBP and HNF-1α. The levels of hepatic IL-6 and IL-18 were significantly decreased in the fucoidan group. Further, the levels of cytochrome P450-2E1 (CYP2E1), glucose-regulated protein (GRP) 78, and 3-nitrotyrosine (3-NT) in hepatic tissues were reduced in the fucoidan group as compared to the model group. Fucoidan significantly reversed the reduction of ileac Farnesoid X receptor (FXR) and fibroblast growth factor 15 (FGF15) levels induced by alcohol-feeding and reduced CYP7A1 (cholesterol 7α-hydroxylase) expression and total bile acid levels in the liver tissue. In addition, fucoidan regulated the structure of gut flora, with increased abundance of and decreased abundance of and as detected by 16S rDNA high-throughput sequencing.
Fucoidan inhibited alcohol-induced steatosis and disorders of bile acid metabolism in mice through the AMPKα1/SIRT1 pathway and the gut microbiota-bile acid-liver axis and protected against alcohol-induced liver injury in vivo.
酒精性肝病是由长期饮酒引起的。在本研究中，我们使用酒精性肝损伤小鼠模型来研究岩藻依聚糖对乙醇诱导的肝损伤和脂肪变性的影响及其潜在机制。
将所有小鼠随机分为四组：1）对照组，2）模型组，3）甘草酸二铵治疗组（200mg/kg体重），4）岩藻依聚糖治疗组（300mg/kg体重）。给小鼠灌胃乙醇8周诱导肝损伤和脂肪变性。
岩藻依聚糖治疗降低了血清丙氨酸氨基转移酶活性、血清总胆固醇水平和肝甘油三酯水平，并改善了肝细胞形态。岩藻依聚糖治疗上调了AMPKα1、SIRT1和PGC-1α的表达，抑制了ChREBP和HNF-1α的表达。岩藻依聚糖组肝组织中IL-6和IL-18水平显著降低。此外，与模型组相比，岩藻依聚糖组肝组织中细胞色素P450-2E1（CYP2E1）、葡萄糖调节蛋白（GRP）78和3-硝基酪氨酸（3-NT）水平降低。岩藻依聚糖显著逆转了酒精喂养诱导的回肠法尼酯X受体（FXR）和成纤维细胞生长因子1纤维母细胞生长因子15（FGF15）水平降低，并降低了肝组织中CYP7A1（胆固醇7α-羟化酶）表达和总胆汁酸水平。此外，岩藻依聚糖调节肠道菌群结构，通过16S rDNA高通量测序检测到 丰度增加， 丰度和 丰度降低。
岩藻依聚糖通过AMPKα1/SIRT1途径和肠道微生物群-胆汁酸-肝脏轴抑制小鼠酒精诱导的脂肪变性和胆汁酸代谢紊乱，并在体内预防酒精诱导的肝损伤。
