中华内分泌代谢杂志
中華內分泌代謝雜誌
중화내분비대사잡지
CHINESE JOURNAL OF ENDOCRINOLOGY AND METABOLISM
2015年
3期
272-276
,共5页
徐嘉妤%敖娜%都健%杨晶%王晓晨
徐嘉妤%敖娜%都健%楊晶%王曉晨
서가여%오나%도건%양정%왕효신
胰升糖素样肽1%非酒精性脂肪肝%内质网应激%大鼠%肌醇需求激酶1α%c-jun氨基末端激酶
胰升糖素樣肽1%非酒精性脂肪肝%內質網應激%大鼠%肌醇需求激酶1α%c-jun氨基末耑激酶
이승당소양태1%비주정성지방간%내질망응격%대서%기순수구격매1α%c-jun안기말단격매
Glucagon-like peptide 1%Non-alcoholic fatty liver disease%Endoplasmic reticulum stress%Rats%Inositol requiring enzyme-1α%c-jun N-terminal kinase
目的 探讨非酒精性脂肪肝(NAFLD)大鼠肝脏组织内质网应激(ERs)相关因子肌醇需求激酶1α(IRE1α)、磷酸化IRE1 α(p-IRE1 α)、c-jun氨基末端激酶(JNK)、磷酸化JNK(p-JNK)的表达情况,观察胰升糖素样肽1(GLP-1)类似物的干预作用.方法 将40只雄性SD大鼠分为正常饮食组(n=15)和高脂饮食组(n=25),喂养12周后,每组取5只评估NAFLD大鼠模型的建立,再将高脂饮食组大鼠分为高脂饮食组(HF,n=10)和GLP-1组(HG,n=10),分别以生理盐水及GLP-1类似物干预4周,测定大鼠体重及生化指标,Western印迹法检测肝组织IRE1α、p-IRE1α、JNK、p-JNK的蛋白表达水平.结果 HF组大鼠的体重、血清甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、丙氨酸转移酶(ALT)、天冬氨酸转移酶(AST)较正常饮食组明显升高(均P＜0.01),高密度脂蛋白胆固醇(HDL-C)明显降低(P＜0.01),p-IRE1α/IRE1α及p-JNK/JNK升高(P＜0.05及P＜0.01),而高脂喂养的大鼠经GLP-1类似物干预后,体重、TG、TC、LDL-C、AST、ALT明显降低(P＜0.05或P＜0.01),HDL-C明显升高(P＜0.01),p-IRE1α/IRE1α及p-JNK/JNK降低(P＜0.05及P＜0.01).结论 GLP-1类似物可能通过调节ERs相关IRE1 α-JNK通路改善肝脏脂肪变性.
目的 探討非酒精性脂肪肝(NAFLD)大鼠肝髒組織內質網應激(ERs)相關因子肌醇需求激酶1α(IRE1α)、燐痠化IRE1 α(p-IRE1 α)、c-jun氨基末耑激酶(JNK)、燐痠化JNK(p-JNK)的錶達情況,觀察胰升糖素樣肽1(GLP-1)類似物的榦預作用.方法 將40隻雄性SD大鼠分為正常飲食組(n=15)和高脂飲食組(n=25),餵養12週後,每組取5隻評估NAFLD大鼠模型的建立,再將高脂飲食組大鼠分為高脂飲食組(HF,n=10)和GLP-1組(HG,n=10),分彆以生理鹽水及GLP-1類似物榦預4週,測定大鼠體重及生化指標,Western印跡法檢測肝組織IRE1α、p-IRE1α、JNK、p-JNK的蛋白錶達水平.結果 HF組大鼠的體重、血清甘油三酯(TG)、總膽固醇(TC)、低密度脂蛋白膽固醇(LDL-C)、丙氨痠轉移酶(ALT)、天鼕氨痠轉移酶(AST)較正常飲食組明顯升高(均P＜0.01),高密度脂蛋白膽固醇(HDL-C)明顯降低(P＜0.01),p-IRE1α/IRE1α及p-JNK/JNK升高(P＜0.05及P＜0.01),而高脂餵養的大鼠經GLP-1類似物榦預後,體重、TG、TC、LDL-C、AST、ALT明顯降低(P＜0.05或P＜0.01),HDL-C明顯升高(P＜0.01),p-IRE1α/IRE1α及p-JNK/JNK降低(P＜0.05及P＜0.01).結論 GLP-1類似物可能通過調節ERs相關IRE1 α-JNK通路改善肝髒脂肪變性.
목적 탐토비주정성지방간(NAFLD)대서간장조직내질망응격(ERs)상관인자기순수구격매1α(IRE1α)、린산화IRE1 α(p-IRE1 α)、c-jun안기말단격매(JNK)、린산화JNK(p-JNK)적표체정황,관찰이승당소양태1(GLP-1)유사물적간예작용.방법 장40지웅성SD대서분위정상음식조(n=15)화고지음식조(n=25),위양12주후,매조취5지평고NAFLD대서모형적건립,재장고지음식조대서분위고지음식조(HF,n=10)화GLP-1조(HG,n=10),분별이생리염수급GLP-1유사물간예4주,측정대서체중급생화지표,Western인적법검측간조직IRE1α、p-IRE1α、JNK、p-JNK적단백표체수평.결과 HF조대서적체중、혈청감유삼지(TG)、총담고순(TC)、저밀도지단백담고순(LDL-C)、병안산전이매(ALT)、천동안산전이매(AST)교정상음식조명현승고(균P＜0.01),고밀도지단백담고순(HDL-C)명현강저(P＜0.01),p-IRE1α/IRE1α급p-JNK/JNK승고(P＜0.05급P＜0.01),이고지위양적대서경GLP-1유사물간예후,체중、TG、TC、LDL-C、AST、ALT명현강저(P＜0.05혹P＜0.01),HDL-C명현승고(P＜0.01),p-IRE1α/IRE1α급p-JNK/JNK강저(P＜0.05급P＜0.01).결론 GLP-1유사물가능통과조절ERs상관IRE1 α-JNK통로개선간장지방변성.
Objective To explore the expressions of endoplasmic reticulum stress (ERs) related factors including inositol requiring enzyme-1α(IRE1αα),p-IRE1 α,c-jun N-terminal Kinase(JNK),and p-JNK in rats with non-alcoholic fatty liver disease,and to investigate the effect of intervention with glucagon-like peptide 1 (GLP-1) analogue.Methods Forty male Sprague-Dawley rats were divided into normal chow group(n =15) and high-fat diet group(n=25).After 12 weeks,5 rats of each group were used to assess the establishment of rat models with non-alcoholic fatty liver disease.Then the high-fat diet group rats were divided into high-fat diet group (HF,n =10) and GLP-1 group(HG,n=10) and treated with normal saline and GLP-1 analogue for4 weeks respectively.Body weight and biochemical markers in rats were measured.The expressions of IRE1α,p-IRE1α,JNK,and p-JNK were measured by Western blot.Results Compared with the NC group,the levels of body weight,plasma triglyceride (TG),total cholesterol (TC),low density lipoprotein-cholesterol (LDL-C),alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in HF group were significantly higher (all P ＜ 0.01),high density lipoprotein-cholesterol(HDL-C) was decreased(P＜0.01),and p-IRE1 α/IRE1 α and p-JNK/JNK were increased(P＜0.05 and P＜0.01).After GLP-1 treatment,body weight,plasma TG,TC,LDL-C,AST,ALT in HF group were significantly lowered(P＜0.05 or P＜0.01),HDL-C was increased(P＜0.01),p-IRE1 α/IRE1 α and p-JNK/JNK were decreased (P＜0.05 and P＜0.01).Conclusion GLP-1 analogue may improve hepatic steatosis via regulating ERs related IRE1 α-JNK signaling pathway.
