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作 者:陈少华[1,2] 于慧[2,3] 王汝霞[4] 冯丽[1,2] 张伟[2] 赵家军[1] 高聆[5]
机构地区:[1]山东大学附属省立医院内分泌科,济南250021 [2]山东大学附属千佛山医院内分泌科,济南250014 [3]淄博市中心医院内分泌科,山东淄博255036 [4]山东省医学科学院药物研究所,济南250062 [5]山东大学附属省立医院中心实验室,济南250021
出 处:《山东大学学报(医学版)》2010年第12期5-10,共6页Journal of Shandong University:Health Sciences
基 金:山东省自然科学基金资助项目(Y2001C12)
摘 要:目的探索长期饮酒对大鼠肝内糖原合成酶激酶-3(GSK-3)、磷酸腺苷激活的蛋白激酶(AMPK)、葡萄糖转运蛋白4(GLUT4)的影响。方法用AMPK激动剂(AICAR)注射大鼠,观察其对糖原、GSK-3β、AMPK的影响。取Wistar大鼠48只,随机分为A、B、C、D组,给予酒精灌胃,对应酒精剂量分别为5g/kg.d、2.5g/kg.d、0.5g/kg.d及0(生理盐水),20周后取其肝组织测GSK-3β、AMPK(AMPKα,P-AMPKα)、GLUT4蛋白和AMPK、GLUT4mRNA的表达以及切片组织GSK-3β的荧光表达。结果注射AICAR大鼠的肝糖原含量增高,GSK-3β、AMPK也较原水平有所变化。服酒精各组GSK-3β荧光信号强,A组更明显,蛋白表达增强;而酒精各组P-AMPKα蛋白表达均明显降低(P均<0.01);GLUT4mRNA和蛋白也降低(P均<0.05)。结论大鼠长期酒精灌胃可能影响GSK-3β、AMPK水平,继而降低肝糖原水平。Objective To investigate influences on glycogen synthase kinase-3β(GSK-3β),AMP-activated protein kinase(AMPK)and glucose transporter type 4(GLUT4)after ethanol feeding for a long time.Methods AMPK activator(AICAR)was injected into rats and influences on hepatic glycogen,GSK-3β and AMPK were observed.48 Wistar rats were randomly divided into 4 groups and fed different doses of ethanol(A,B,C,5,2.5,0.5 g/kg·d)or normal saline(D)for 20 weeks.Then GSK-3β,AMPK(AMPKα,P-AMPKα)and GLUT4 proteins,AMPK and GLUT4 mRNAs,and glycogen in the liver were measured.Results AICAR injection resulted in high expressions of glycogen and phosphorylated AMPKα(P-AMPKα)and lower expression of GSK-3β in the liver of rats.In ethanol-fed rats,GSK-3β was over-expressed in the three ethanol feeding groups,especially in group A,while P-AMPKα protein expression was significantly decreased(P〈0.01).Decreased mRNA and protein expressions of GLUT4 were found(P〈0.05).Conclusion Long-time ethanol feeding affected GSK-3β and AMPK levels,and then decreased the level of hepatic glycogen.
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