鱼油对高果糖高脂高胆固醇饮食诱导的小鼠非酒精性脂肪性肝炎的影响

摘要

Objective The aim of this study was to investigate how fish oil rich diet affected nonalcoholic steatohepatitis (NASH) induced by high fructose high fat high cholesterol diet in mouse.Methods 45 C3H mice aged 6 weeks were divided into 3 groups:normal diet group (control),lard rich diet group as model group (lard),fish oil rich diet (fish oil).Mice were sacrificed at the end of week 4,8,16,5 mice at each time point.Blood and liver were collected to test biochemical parameters,liver index,liver pathology and mRNA expression of inflammation associated gene.Results total cholesterol (TC) and serum ALT,AST increased significantly comparing to control (P ＜ 0.001),fish oil intervention inhibited these increases (P ＜0.05).The expression of monocyte chemotactic protein-1 (MCP-1) was upregulated,most dramatically at week 4,in lard group.While the mRNA level of MCP-1 is lower in fish oil group than lard group.TNF-α and TGF-β gene expression also rise at week 8,this trend diminished in fish oil group.HE staining showed apparent steatosis and inflammation infiltration at week 8 and 16 in lard group,while inflammation infiltration was weaker in fish oil group.The expression of kupffer cell marker gene CD68 elevated in lard group,fish oil diet down regulated this elevation.Conclusion Fish oil was able to protect liver from NASH related injury induced by high fructose high fat high cholesterol diet.%目的 探讨鱼油对高果糖高脂高胆固醇饮食诱导的非酒精性脂肪性肝炎(NASH)的干预效果.方法 45只6周龄C3H小鼠随机分为3组:普通饲料组(对照组)、猪油组(模型组)、鱼油组(干预组).分别在4、8、16周末处死小鼠,每组次5只.观察血生化指标,肝指数(肝脏湿重/体重)、肝脏炎症程度及炎症相关基因的表达情况.结果 16周末模型组血清总胆固醇(TC)和血清ALT及AST比对照组显著升高,鱼油组TC和ALT、AST水平与猪油组相比明显下降.基因表达检测显示猪油组单核细胞趋化因子MCP-1的表达在第4周显著上调(P＜0.05),而鱼油组MCP-1mRNA水平明显低于猪油组(P＜0.05).猪油组TNF-α和TGF-β在第8周表现出上调趋势,鱼油组对此上调有抑制作用.HE染色显示猪油组和鱼油组在第8、16周出现明显的脂肪变及炎症细胞浸润.猪油组的炎症浸润较鱼油组显著.肝库普弗细胞的标记物CD68在8周(P＜0.05)、16周表达上调,鱼油组对此上调有抑制作用.结论 鱼油能减轻高果糖高脂高胆固醇诱导的小鼠NASH肝损伤.