β在糖尿病肾病小鼠肾组织中的分布和表达.pdf

第43卷第2期第130页
华中科技大学学报(医学版)
Val.43No.2P.130
014年4月
Acta Med Univ Sci Technol Huazhong
2014
糖原合成酶激酶3/β在糖尿病肾病小鼠肾组织
中的分布和表达
冀情倩2,李永霞,金文敏',段秋红3,姚丽君1?
华中科技大学同济医学院附属协和医院肾内科,武汉430022
湖北省中山医院肾内科,武汉430033
华中科技大学同济医学院基础医学院生物化学与分子生物学系,武汉430030
摘要:目的研究糖原合成酶激酶-3/3(GSK-3a/)在糖尿病肾病(DN)小鼠肾组织中的不同分布和表达。方法
链脲霉素(STZ)腹腔注射建立小鼠DN模型,成模后2周收集小鼠血、尿标本及肾组织,采用激光共聚焦技术检测GSK
3a/β在肾组织中的分布,免疫印迹法检测GSK-3a/β、 podocin及p- catenin在肾组织中的表达。结果①GSK-3主要分
布于小鼠肾小球、近曲小管、外髓髖袢升支粗段及内髓集合管,而GSK3a仅见于内髓集合管;②DN小鼠内髓集合管上
皮细胞中GSK-3a与β发生转位变化,内髓GSK-3a、磷酸化GSK-3a以及肾皮质磷酸化GSK-3的表达均明显増加;③
DN小鼠肾皮质中B- catenin的表达明显减少。结论GSK3a与在DN发病中扮演不同角色,其中GSK33可能通过
影响β- catenin表达参与DN肾小球损伤的发生
关键词:糖原合成酶激酶-3;糖尿病肾病;β- catenin
中图分类号:R692.DOI:10.3870/,issn.1672-0741.2014.02.003
Different Distribution and Expression of Glycogen Synthase Kinase-3/B
in Kidney of Diabetic Nephropathy Mice
Ji Qiangian'=, Li Yongxia Jin Wenmin et al
Departments of Nephrology, Union Hospital, Tongji Medical College, Huazhong
University of Science and Technology, Wuhan 430022, China
'Department of Nephrology, Zhongshan Hospital of Hubei Province, Wuhan 430033, China
Abstract Objective To investigate the different distribution and expression pattern of glycogen synthase kinase-3/3
(GSK-3A/B)in the kidney of diabetic nephropathy (DN) mice. Methods C57BL/6 mice were divided into control group and DN
group. The mice in DN group were intraperitoneally injected with streptozotocin. Blood, urine and renal tissues of the mice in
each group were harvested 2 weeks later. The localization of GSK-8A/3 was determined by laser scanning confocal immunofluo
rescence microscopy. The expression of podocin, -catenin, GSK-3A/8 was detected by immunoblotting Results O GSK-3 was
pressed in glomeruli, proximal tubules, medullary thick ascending limbs in the outer medulla and
collecting ducts, while GSK-3A was only expressed in inner medullary collecting ducts in normal mice; ) GSK-3 and were
translocated to the luminal membrane of the epithelial cells in the inner medullary collecting ducts of DN mice, and the expres
sion level of phospho-gsk-3b(Ser9/21)in the cortex, that of GSK-3A and phospho-gsk-3a in the inner mudulla were signifi
cantly higher in DN mice than those in normal mice; the expression level of g catenin in the cortex of DN mice was significant-
ly decreased. Conclusion GSK-3Q and B play different roles in the development of DN. GSK-3B may be involved in the develop-
ment of DN by inhibiting the expression of -catena
Key words glycogen synthase kinase-3; diabetic nephropathy; -catenin
糖尿病肾病( diabetic nephropathy,DN)是糖尿代谢调节中的关键激酶,在细胞生长、增殖、潢亡等
病微血管病变并发症之一,其发病率正逐年升高,已多种信号通路中发挥重要作用い的,其中GSK-3的
成为慢性肾功能衰竭最重要的致病因素。糖原合成磷酸化使其活性受抑。多项研究表明,GSK-3
酶激酶-3( glycogen synthase kinase3,GSK-3)是糖与DN蛋白尿以及多尿的发生发展密切相关?,但
其具体的致病途径和关键环节还不甚清楚
“国家自然科学基金资助项目(No.81370818),湖北省自然科学基金
GSK-3家族在哺乳动物体内有2个亚型:GSK
资助项目(No.2013CFB176
冀情倩,女,1986年生,住院医师,医学硕士,E-mail:-13720163521
3a和GSK-3,迄今为止有关GSK-3a与β在正常以
及DN小鼠肾组织的分布、表达未见报道,为此,本
?通讯作者, Corresponding author,E-mail: dryli(の hotmail,com