n-3多不饱和脂肪酸对大鼠酒精性脂肪肝炎性反应及肝纤维化的影响  

Effects of n-3 polyunsaturated fatty acids on alcoholic fatty liver inflammation and liver fibrosis in rats

作　　者：沈云海 付明生 刘秀平[1] 冯洁[1] 潘勤聪[1] Shen Yunhai;Fu Mingsheng;Liu Xiuping;Feng Jie;Pan Qincong(The Fifth People’s Hospital of Fudan University,Shanghai 201102,China)

机构地区：[1]上海市复旦大学第五人民医院消化内科

出　　处：《疑难病杂志》2020年第2期180-183,189,共5页Chinese Journal of Difficult and Complicated Cases

摘　　要：目的探讨n-3多不饱和脂肪酸(n-3PUFA)对大鼠酒精性脂肪肝炎性反应、肝纤维化的影响及机制。方法选择40只雄性SD大鼠,编号后采用随机数字表法分为对照组、模型组、n-3PUFA组、n-3PUFA+内毒素(LPS)组,每组各10只,对照组给予正常饲料及每日生理盐水灌胃,另外3组大鼠采用酒精灌胃的方式建立酒精性脂肪肝模型,n-3PUFA组给予n-3PUFA干预、n-3PUFA+LPS组给予n-3PUFA及Toll样受体4(TLR4)激动剂LPS干预。8周后,处死大鼠取肝和血清标本,观察各组大鼠肝组织病理变化,测定4组大鼠肝脏中TLR4、核因子-κB (NF-KB)、肿瘤坏死因子-α(TNF-α)、单核细胞趋化蛋白-1(MCP-1)和白细胞介素1(IL-1)的表达水平,以及血清中转化生长因子-β1(TGF-β1)、透明质酸(HA)和Ⅳ型胶原(C-Ⅳ)的含量。结果对照组大鼠肝组织结构正常,模型组可见弥漫性肝细胞脂肪变性,n-3PUFA组肝细胞脂肪变性减轻,而n-3PUFA+LPS组肝组织脂肪变性较n-3PUFA组加重。模型组大鼠肝脏中TLR4、NF-κB、TNF-α、MCP-1和IL-1的mRNA表达水平及血清中TGF-β1、HA和C-Ⅳ的含量高于对照组,差异有统计学意义(P<0.05);n-3PUFA组肝脏中TLR4、NF-κB、TNF-α、MCP-1和IL-1的mRNA表达水平及血清中TGF-β1、HA和C-Ⅳ的含量低于模型组,差异有统计学意义(P <0.05);n-3PUFA+LPS组肝脏中TLR4、NF-κB、TNF-α、MCP-1和IL-1的mRNA表达水平及血清中TGF-β1、HA和C-Ⅳ的含量高于n-3PUFA组,差异有统计学意义(P<0.05)。结论 n-3PUFA对大鼠酒精性脂肪肝炎性反应及肝纤维化具有抑制作用,且该作用与TLR4/NF-κB信号通路阻断有关。Objective To investigate the effect and mechanism of n-3 polyunsaturated fatty acids(n-3 PUFA) on alcoholic fatty liver inflammation and liver fibrosis in rats.Methods Forty male SD rats were selected and numbered into a control group,a model group,an n-3 PUFA group,and an n-3 PUFA+endotoxin(LPS) group,with 10 rats in each group.The control group was given normal feed and daily saline.The other three groups of rats were given alcoholic fatty liver model by gastric administration.The n-3 PUFA group was given n-3 PUFA intervention,and the n-3 PUFA+LPS group was given n-3 PUFA and Toll-like receptor 4(TLR4) agonist LPS intervention.After 8 weeks,the rats were sacrificed to obtain liver and serum samples.Observe the pathological changes of liver tissue in each group of rats,and determine the TLR4,nuclear factorκB(NF-κB),tumor necrosis factor α(TNF-a),monocyte chemotactic protein 1(MCP-1),and leukocyte mediator The expression level of IL-1 and the contents of serum transforming growth factor β1(TGF-β1),hyaluronic acid(HA) and type Ⅳcollagen(C-Ⅳ).Results In the control group,the liver tissue structure was normal,and in the model group,diffuse hepatocyte steatosis was seen,while in the n-3 PUFA group,hepatocyte steatosis was reduced.But the liver tissue steatosis in n-3 PUFA+LPS group was worse than that in n-3 PUFA group.The expression levels of TLR4,NF-κB,TNF-a,MCP-1 and IL-1 in the liver of the model group rats and the contents of TGF-β1,HA and CⅣ in the serum were higher than those in the control group,the differences were statistically significant(P <0.05).The mRNA expression levels of TLR4,NF-κB,TNF-a,MCP-1 and IL-1 in the liver and serum TGF-β1,HA and C IV in the n-3 PUFA group were lower than those in the model group,and the differences were statistically significant(P <0.05).The expression levels of TLR4,NF-κB,TNF-a,MCP-1 and IL-1 in the liver and serum levels of TGF-β1,HA and C-Ⅳ in the n-3 PUFA+LPS group were higher than those in the n-3 PUFA group,the differences were statistically signifi

关 键 词：酒精性脂肪肝 N-3多不饱和脂肪酸 TOLL样受体4 炎性反应 肝纤维化 大鼠 

分 类 号：R575[医药卫生—消化系统]