消退素D1改善2型糖尿病小鼠肝脏脂肪沉积

Resolvin D1 improves liver fat deposition in type 2 diabetic mice

目的探讨消退素D1对2型糖尿病(T2DM)小鼠肝脏脂肪沉积的影响及其机制。方法30只C57BL/6J雄性小鼠随机分为对照组(Con组)10只和高脂饮食组(DM组)20只,喂养8周后DM组小鼠腹腔注射链脲霉素制备T2DM小鼠模型,模型成功后从DM组随机选取10只小鼠给予消退素D1(RvD1)干预(DM+RvD1组),3周后测定胰岛素抵抗指数(HOMA-IR)。检测小鼠总胆固醇(TC)和甘油三酯(TG)水平,以及各组肿瘤坏死因子(TNF)-α、白介素(IL)-6含量。免疫印迹实验测定肝脏组织中NF-κB p65、p-AKT、Foxo1、p-Foxo1水平。结果与Con组比较,DM组HOMA-IR升高(P<0.05);与DM组比较,DM+RvD1组HOMA-IR下降(P<0.05)。与Con组比较,DM组TG和TC水平均升高(P<0.05);与DM组比较,DM+RvD1组TG和TC水平下降(P<0.05)。与Con组比较,DM组肝组织NF-κB p65、Foxo1表达均升高(P<0.05);与DM组比较,DM+RvD1组NF-κB p65和Foxo1水平均下降(P<0.05),TNF-α和IL-6相应降低(P<0.05)。与Con组比较,DM组肝组织p-AKT和p-Foxo1表达下降(P<0.05);与DM组比较,DM+RvD1组两者升高(P<0.05)。结论RvD1的应用可抑制T2DM小鼠肝脏NF-κB激活,降低炎症反应,提升p-AKT水平并使磷酸化Foxo1升高缓解肝脏脂肪沉积。

Objective To explore the effect and mechanism of resolvin D1 on liver fat deposition in type 2 diabetic mellitus(T2DM)mice.Methods Thirty C57BL/6J male mice were randomly divided into Con group(n=10,normal diet),and DM group(n=20,high-fat diet).After 8 weeks of feeding,the mice in DM group were injected with streptozotocin(STZ)to establisha T2DM model.Ten mice were treated with resolvin D1 in DM+RvD1group.After 3 weeks resolvin D1 intervention,the insulin resistance index(HOMA-IR)of mice in each group was tested.Serum levels of triglyceride,total cholesterol,tumor necrosis factor-α,and interleukin-6 were detected.The expression levels of NF-κB p65,p-AKT,Foxo1,and p-Foxo1 in liver tissues was detected by Western blot.Results Compared with Con group,HOMA-IR was significantly increased in DM group(P<0.05).Compared with DM group,HOMA-IR was significantly decreased in DM+RvD1 group(P<0.05).Compared with Con group,TG and TC levels were increased in DM group(P<0.05).Compared with DM group,TG and TC levels were reduced in DM+RvD1 group(P<0.05).Compared with Con group,NF-κB p65 and Foxo1 expression levels in liver tissues were increased in DM group(P<0.05).Compared with DM group,NF-κB p65 and Foxo1 levels were decreased in DM+RvD1 group(P<0.05),TNF-αand IL-6 were significantly decreased in DM+RvD1 group(P<0.05).Compared with Con group,the expression of p-AKT and p-Foxo1 was decreased in DM group(P<0.05),and compared with DM group,the expression of p-AKT and p-Foxo1 was increased in DM+RvD1 group(P<0.05).Conclusion Resolvin D1 could inhibit the NF-κB activation in liver tissue of diabetes mice,reduce the inflammation factors,increase the levels of p-AKT and p-Foxo1 to relieve the liver fat deposition.