利拉鲁肽对非酒精性脂肪肝大鼠肝脏组织中胰岛素JNK1信号通路的影响  

Effects of liraglutide on insulin JNK1 signaling pathway in liver tissues of rats with nonalcoholic fatty liver disease

作　　者：张梅[1] 石秀英[2] 李林娟[1] 薛亚妮[3] ZHANG Mei;SHI Xiu-ying;LI Lin-juan;XUE Ya-ni(Department of General Medicine,Dongguan Branch of Yan’an University Affiliated Hospital,Yan’an 716000,Shaanxi,China;Department of Ultrasound Diagnosis,Dongguan Branch of Yan’an University Affiliated Hospital,Yan’an 716000,Shaanxi,China;Department of Respiratory Medicine,Yan’an University Affiliated Hospital,Yan’an 716000,Shaanxi,China)

机构地区：[1]延安大学附属医院东关分院综合内科,陕西延安716000 [2]延安大学附属医院东关分院超声诊断科,陕西延安716000 [3]延安大学附属医院呼吸内科,陕西延安716000

出　　处：《现代消化及介入诊疗》2019年第4期374-378,共5页Modern Interventional Diagnosis and Treatment in Gastroenterology

摘　　要：目的探究利拉鲁肽对非酒精性脂肪肝(NAFLD)大鼠肝脏组织中胰岛素JNK1信号通路的影响。方法选取40只6周龄SPF级大鼠,采用高脂饮食喂养12周建立NAFLD大鼠模型。将NAFLD大鼠随机分为空白对照组(control)、模型组(model)、低剂量利拉鲁肽组(low lira)和高剂量利拉鲁肽组(high lira)。利拉鲁肽干预18 d后,测量大鼠体质量及肝指数变化;全自动生化分析仪测定大鼠血清丙氨酸氨基转移酶(ALT)、空腹血糖(FBG)、甘油三酯(TG)、总胆固醇(TC)和血清胰岛素(FINS)变化;酶联免疫吸附法测定大鼠肝组织中肿瘤坏死因子(TNF-α)、超氧化物歧化酶(SOD)、丙二醛(MAD)及游离脂肪酸(FFAs)含量; Western blot检测大鼠肝脏组织中胰岛素受体(IR)、磷酸化胰岛素受体底物1(p-IRS1)、C-Jun氨基端激酶1(JNK1)及磷酸化C-Jun氨基端激酶1(p-JNK1)表达情况; HE染色观察大鼠肝脏组织病理学变化。结果与对照组相比,模型组大鼠体质量,肝指数,血清ALT、TG、TC、FINS、TNF-α、MAD、FFAs含量,p-IRS1、JNK1、p-JNK1蛋白表达量显著升高,SOD含量显著降低,差异有统计学意义(P <0. 01);血清FBG含量和IR蛋白表达量无显著变化(P> 0. 05);相比模型组,利拉鲁肽组大鼠体质量,肝指数,血清ALT、TG、TC、FINS、TNF-α、MAD、FFAs含量,p-IRS1、JNK1、p-JNK1蛋白表达量显著降低,且高剂量组显著低于低剂量组(P <0. 01); SOD含量显著升高,且高剂量组显著高于低剂量组(P <0. 01);血清FBG含量和IR蛋白表达量无显著变化(P> 0. 05)。结论利拉鲁肽可以缓解大鼠脂肪肝的发展,其作用机制可能与抑制JNK1信号通路及JNK1磷酸化相关,且在一定范围内呈浓度依赖性。Objective To explore the effects of liraglutide on insulin JNK1 signaling pathway in liver tissues of rats with nonalcoholic fatty liver disease.Methods Forty 6-week-old SPF rats were fed with a high-fat diet for 12 weeks to establish the NAFLD rat model.NAFLD rats were randomly divided into blank control group(control),model group(model),low dose liraglutide group(low lira)and high dose liraglutide group(high lira).After 18 days of intervention with liraglutide,the changes of body weight and liver indexes were measured.The serum alanine aminotransferase(ALT),fasting blood glucose(FBG),triglyceride(TG),total cholesterol(TC)and serum insulin(FINS)were measured by automatic biochemical analyzer.The levels of tumor necrosis factor(TNF-α),superoxide dismutase(SOD),malondialdehyde(MAD)and free fatty acid(FFAs)in rat liver tissues were detected by enzyme-linked immunosorbent assay.Western blot was used to detect the expression levels of insulin receptor(IR),phosphorylated insulin receptor substrate 1(p-IRS1),C-Jun N-terminal kinase 1(JNK1)and phosphorylation C-Jun N-terminal kinase 1(p-JNK1)in rat liver tissues.The pathological changes in rat liver tissues were observed by HE staining.Results Compared with control group,the body weight,liver indexes,levels of serum ALT,TG,TC,FINS,TNF-α,MAD and FFAs,and protein expression levels of p-IRS1,JNK1 and p-JNK1 in model group were increased significantly while the SOD level was decreased significantly(P<0.01).There were no significant changes in the serum FBG level and IR protein expression level(P>0.05).Compared with model group,the body weight,liver indexes,levels of serum ALT,TG,TC,FINS,TNF-α,MAD and FFAs,and protein expression levels of p-IRS1,JNK1 and p-JNK1 in liraglutide groups were decreased significantly,and the indexes in high dose group were significantly lower than those in low dose group(P<0.01).The SOD level was increased significantly,and the level in high dose group was significantly higher than that in low dose group(P<0.01),and there were no significant ch

关 键 词：非酒精性脂肪肝 利拉鲁肽 胰岛素 JNK1信号通路 

分 类 号：R575[医药卫生—消化系统]