糖原合成酶激酶-3a／b在糖尿病肾病小鼠肾组织中的分布和表达

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/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-3α/βwas determined by laser scanning confocal immunofluo-rescence 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-3α was only expressed in inner medullary collecting ducts in normal mice ;② GSK-3α and β 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-3β (Ser9/21) in the cortex ,that of GSK-3αand phospho-GSK-3αin the inner mudulla were signifi-cantly higher in DN mice than those in normal mice ;③the expression level of β-catenin in the cortex of DN mice was significant-ly decreased.Conclusion GSK-3αandβplay different roles in the development of DN.GSK-3βmay be involved in the develop-ment of DN by inhibiting the expression of β-catenin.%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。