摘要目的 通过建立大鼠非酒精性脂肪性肝病(NAFLD)模型,观察胰升血糖素样肽1(GLP-1)对NAFLD大鼠氧化应激损伤的干预效应.方法 60只雄性SD大鼠分为正常饮食组(NC组,n=15)和高脂饮食组(HF组,n=45),12周末评估NAFLD模型的建立.NC组给予等渗盐水干预,HF组再分为等渗盐水组(NS组,n=10),低剂量GLF-1组(LG组,n=10),中剂量GLP-1组(MG组,n=10),高剂量GLP-1组(HG组,n=10),给予等渗盐水及不同剂量(50μg/kg,100μg/kg,200 μg/kg) GLP-1进行干预,4周后检测血清生物化学指标(甘油三酯、总胆固醇、高密度脂蛋白、低密度脂蛋白、ALT、AST),肝组织超氧化物歧化酶、丙二醛及细胞色素氧化酶P450 2E1 (CYP2E1)mRNA和蛋白含量.两个样本均数比较采用t检验或近似t检验,多个样本均数比较采用LSD检验或Dunnett T3检验.结果 NS组超氧化物歧化酶水平较NC组显著降低[(165.81±11.64) U/mg对比(192.89±16.53) U/mg,P＜ 0.05],丙二醛水平显著升高[(7.30±1.79)nmol/mg对比(3.10±1.30)nmol/mg,P＜0.05],CYP2E1 mRNA及蛋白含量亦明显升高(P＜0.05).经过GLP-1干预后,与NS组比较,LG、MG、HG组大鼠肝组织超氧化物歧化酶水平呈升高趋势[(171.44±9.80) U/mg对比(177.66±14.77)对比(186.17±15.43) U/mg,仅HG组,P＜0.05],MDA水平明显降低[(5.16±1.45)nmol/mg对比(4.08±1.22) nmol/mg对比(3.31±1.14)nmol/mg,P＜0.05],CYP2E1 mRNA和蛋白水平亦呈降低趋势(CYP2E1 mRNA含量仅HG组差异有统计学意义,P＜0.05;CYP2E1蛋白含量在MG、HG组差异均有统计学意义,P值均＜0.05). 结论 GLP-1可改善肝组织脂质沉积,减轻NAFLD大鼠氧化应激损伤.

abstractsObjective To investigate the effects of glucagon-like peptide-1 (GLP-1) on liver oxidative stress injury using a rat model of non-alcoholic fatty liver disease.Methods Sixty male Sprague-Dawley rats were fed 12 weeks of either a diet of normal chow (NC),for use as controls (n =15) or high-fat chow (HF),for use as models (n =45).The NC rats were administered normal saline,while the HF rats were treated with either normal saline (NS),for use as untreated model controls (n =10),low-dose GLP-1 (LG,50 μtg/kg; n =10),mid-dose GLP-1 (MG,100 μtg/kg; n =10),or high-dose GLP-1 (HG,200 μg/kg; n =10); all treatments lasted for 4 weeks.The rats' weight,levels of serum biochemical markers (triglycerides,total cholesterol,high-density lipoproteincholesterol,low-density lipoprotein-cholesterol,alanine arninotransferase,and aspartate aminotransferase),levels of superoxide dismutase (SOD) and malondialdehyde (MDA),and expression of CYP2E1 mRNA and protein in liver homogenates were measured.The F test,t-test,least significant difference test and Dunnett's T3 test were used for statistical analyses.Results Compared with the NC group,the rars in the NS group showed significantly lower SOD (165.81±11.64 vs.192.89±16.53 U/mg,P ＜ 0.05),significantly higher MDA (7.30±1.79 vs.3.10±1.30 nmol/ mg,P ＜ 0.05),and significantly higher expressions of CYP2E1 mRNA and protein (both P ＜ 0.05).After GLP1 treatment,the rats in the LG,MG and HG groups showed increased levels of SOD (compared to the NS group; 171.44±9.80 vs.177.66±14.77 vs.186.17±15.43 U/mg; only the HG group had P ＜ 0.05),significantly decreased levels of MDA (compared to the NS group; 5.16±1.45 vs.4.08±1.22 vs.3.31±1.14 nmol/mg; allP＜ 0.05],and decreased levels of CYP2E1 mRNA and protein expressions (CYP2E1 mRNA:only the HG group had P ＜ 0.05; CYP2E1 protein:both the MG and HG groups hadP ＜ 0.05).Conclusion GLP-1 treatment can improve oxidative stress injury,suggesting its potential as a therapeutic agent for non-alcoholic fatty liver disease.