髓样细胞触发性受体1对非酒精性脂肪肝小鼠炎症反应和脂质的影响及其机制

Effects and mechanism of TREM-1 on inflammatory response and lipid metabolism in mice with nonalcoholic fatty liver disease

目的分析髓样细胞触发性受体1(TREM-1)在非酒精性脂肪肝(NAFLD)中的作用及其机制。方法油酸处理后的HepG2细胞,分为模型组、过表达组、干扰A组、干扰B组和阴性对照组。制备NAFLD小鼠模型,随机分成核因子-κB(NF-κB)抑制组、蛋白酶B(AKT)抑制组、敲除A组、敲除B组和空载体组。PCR检测各组肝组织炎症因子和TREM-1的表达,油红O染色检测脂肪积聚。Western印迹检测TREM-1和信号通路蛋白的表达,HE染色检测肝组织变化。结果TREM-1在NAFLD小鼠肝组织[(0.936±0.127)比(0.432±0.105)]和油酸处理后的HepG2细胞中均表达升高。油酸处理后的HepG2细胞中,过表达TREM-1时炎症因子表达增加,脂滴增多;抑制TREM-1表达炎症因子表达降低,脂滴减少。NAFLD小鼠敲除TREM-1和抑制NF-κB活化减少肝细胞炎症因子表达和减轻肝组织损伤;敲除TREM-1和抑制AKT活化,减少肝组织脂滴聚积。结论NAFLD小鼠模型肝组织中TREM-1过表达通过调控NF-κB和AKT信号通路,调节炎症因子表达和脂肪累积。TREM-1可能为治疗NAFLD的作用靶点。

Objective Analysis of the effect of triggering receptor-1 expressed on myeloid cells(TREM-1)in nonalcoholic fatty liver disease(NAFLD)and the mechanism.Methods The oleic acid-treated HepG2 cells were divided into model group,overexpression group,interference group A,interference group B and negative control group.The mouse model of NAFLD was generated and randomly divided into(nuclear factor-κB)NF-κB inhibition group,protein kinase B(AKT)inhibition group,knockout group A,knockout group B and control group.The expression of inflammatory factors and TREM-1 in liver tissue was detected by PCR,and fat accumulation was detected by oil red O staining.Western blotting was used to detect the expression of TREM-1 and signaling pathway proteins,and HE staining was used to detect liver tissue changes.Results TREM-1 was up-regulated in liver tissue of NAFLD mice[(0.936±0.127)vs.(0.432±0.105)]and in oleic acid-treated HepG2 cells.In oleic acid-treated HepG2 cells,overexpression of TREM-1 increased inflammatory factor expression and increased lipid droplets;inhibition of TREM-1 expression decreased inflammatory factor expression,and lipid droplets decreased.Knockout of TREM-1 and inhibition of NF-κB in NAFLD mice reduced hepatocyte inflammatory factor expression and reduced liver damage;knockout of TREM-1 and inhibition of AKT reduced liver tissue lipids and drops accumulate.Conclusions The overexpression of TREM-1 in NAFLD mice liver tissue can regulate inflammatory factor expression and lipid droplets through NF-κB and AKT signal pathway.TREM-1 might be a potential therapeutic target of NAFLD.