中文摘要：

目的研究糖原合成酶激酶-3α/β（GSK-3α/β）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-3α/β在肾组织中的分布,免疫印迹法检测GSK-3α/β、podocin及β-catenin在肾组织中的表达。结果①GSK-3β主要分布于小鼠肾小球、近曲小管、外髓髓袢升支粗段及内髓集合管,而GSK-3α仅见于内髓集合管;②DN小鼠内髓集合管上皮细胞中GSK-3α与β发生转位变化,内髓GSK-3α、磷酸化GSK-3α以及肾皮质磷酸化GSK-3β的表达均明显增加;③DN小鼠肾皮质中β-catenin的表达明显减少。结论 GSK-3α与β在DN发病中扮演不同角色,其中GSK-3β可能通过影响β-catenin表达参与DN肾小球损伤的发生。

英文摘要：

Objective To investigate the different distribution and expression pattern of glycogen synthase kinase-3α/β（GSK-3α/β）in the kidney of diabetic nephropathy（DN）mice.Methods C57BL/6mice 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 2weeks later.The localization of GSK-3α/βwas determined by laser scanning confocal immunofluorescence microscopy.The expression of podocin,β-catenin,GSK-3α/βwas detected by immunoblotting.Results ① GSK-3βwas predominantly expressed in glomeruli,proximal tubules,medullary thick ascending limbs in the outer medulla and inner medulla collecting ducts,while GSK-3αwas only expressed in inner medullary collecting ducts in normal mice;②GSK-3αandβwere translocated to the luminal membrane of the epithelial cells in the inner medullary collecting ducts of DN mice,and the expression level of phospho-GSK-3β（Ser9/21）in the cortex,that of GSK-3αand phospho-GSK-3αin the inner mudulla were significantly higher in DN mice than those in normal mice;③the expression level ofβ-catenin in the cortex of DN mice was significantly decreased.Conclusion GSK-3αandβplay different roles in the development of DN.GSK-3βmay be involved in the development of DN by inhibiting the expression ofβ-catenin.