长期酒精灌胃对大鼠肝GSK-3β及AMPK水平的影响

山东大学学报(医学版) ›› 2010, Vol. 48 ›› Issue (12): 5-10.

长期酒精灌胃对大鼠肝GSK-3β及AMPK水平的影响

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

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

收稿日期:2010-06-13 发布日期:2010-12-16
通讯作者: 高聆,教授, 主要从事药理、内分泌及代谢疾病研究。E-mail:gaoling1@medmail.com.cn
作者简介:陈少华（1962- ），男，主任医师，研究方向为内分泌及代谢疾病的防治。
基金资助:
山东省自然科学基金资助项目（Y2001C12）

Influence of long-term ethanol feeding on glycogen synthase kinase-3β and AMP-activated protein kinase in Wistar rats

CHEN Shao-hua1, 2, YU Hui2, 3, WANG Ru-xia4, FENG Li1，2, Zhang Wei2, ZHAO Jia-jun1, GAO Ling5

1. Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China;
2. Department of Endocrinology, Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, China;
3. Department of Endocrinology, Zibo Central Hospital, Zibo 255036, Shandong, China;
4. Department of Pharmacology, Shandong Academy of Medical Sciences, Jinan 250062, China;
5. Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China

Received:2010-06-13 Published:2010-12-16

摘要/Abstract

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及零(生理盐水)，20周后取其肝组织测GSK-3β、AMPK(AMPKα, P-AMPKα)、GLUT4蛋白和AMPK、GLUT4 mRNA的表达以及切片组织GSK-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。

关键词: 酒精；糖原合成酶激酶-3；磷酸腺苷激活的蛋白激酶；糖原；大鼠,Wistar

Abstract:

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: feeding different doses of ethanol (A,B,C, 5,2.5, 0.5g/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 the P-AMPKα protein expression was significantly decreased(P<0.01). The 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.

Key words: Ethanol; Glycogen synthese kinase-3; 5′ AMP activated protein kinase; Glycogen; Rat, Wistar

中图分类号:

R575.5

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. 长期酒精灌胃对大鼠肝GSK-3β及AMPK水平的影响[J]. 山东大学学报(医学版), 2010, 48(12): 5-10.

CHEN Shao-hua1, 2, YU Hui2, 3, WANG Ru-xia4, FENG Li1，2, Zhang Wei2, ZHAO Jia-jun1, GAO Ling5. Influence of long-term ethanol feeding on glycogen synthase kinase-3β and AMP-activated protein kinase in Wistar rats[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2010, 48(12): 5-10.

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