利拉鲁肽改善糖尿病小鼠肝脏衰老和纤维化的研究

Lilaglutide improved hepatocyte senescence and liver fibrosis in diabetic mice

目的探讨利拉鲁肽对DM小鼠肝脏损伤的改善作用及对肝脏纤维化、衰老和氧化应激的影响。方法30只C57BL/6J小鼠随机分为正常对照(Con)组,模型组(Mod)和利拉鲁肽组(Lir),每组各10只。Western blot法检测衰老标志性分子p21、p16、肿瘤抑制蛋白(p53)及炎症因子TNF-α、IL-1β蛋白表达,Masson和天狼猩红染色分析利拉鲁肽对肝脏纤维化的影响,比较各组活性氧簇(ROS)、超氧化物歧化酶(SOD)、丙二醛(MDA)氧化应激指标。结果Mod组TNF-α、IL-6、IL-1β、p16、p21、p53、有丝分裂抑制因子、TNF-α、IL-6、IL-1β、核苷酸结合寡聚化结构域样受体蛋白3蛋白和α-平滑肌肌动蛋白表达高于Con、Lir组(P<0.05)。Mod组ROS、MDA高于Con、Lir组,SOD、谷胱甘肽过氧化物酶低于Con、Lir组(P<0.05)。Mod组天狼猩红染色阳性面积、Masson染色阳性面积高于Con、Lir组(P<0.05)。结论利拉鲁肽可缓解肝脏衰老、炎症和纤维化,对DM造成的肝脏损伤具有保护作用。

Objective To investigate the effect of Liraglutide on alleviating the liver injury inmice with DM,and to evaluate the effects of Liraglutide on liver fibrosis,liver aging and liver oxidative stress.Methods Thirty C57BL/6J mice were randomly divided into normal control group(Con),model group(Mod)and Liraglutide group(Lir),with 10 mice in each group.The expressions of p21,p16,p53,inflammatory factors TNF-αand IL-1βwere detected by Western blot.The effects of Liraglutide on liver fibrosis were analyzed by Masson and Sirius scarlet staining.The oxidative stress Lndexes of reactive oxygen species(ROS),superoxide dismutase(SOD)and malondialdehyde(MDA)were compared among the groups.Results The expressions of TNF-α,IL-6,IL-1β,NLRP3,p16,p21,p53,p15,TNF-α,IL-6,IL-1β,NLRP3 andα-SMA were higher in Mod group than in Con and Lir groups(P<0.05).ROS and MDA were higher,while SOD and GSH-PX were lower in Mod group than in Con and Lir group(P<0.05).The positive areas of Sirius scarlet and Masson staining were higher in Mod group than in Con and Lir groups(P<0.05).Conclusions Liraglutide can alleviate liver aging,inflammation and fibrosis,and has protective effect on liver injury caused by DM.