重庆医学2025，Vol.54Issue(12)：2774-2781,8.DOI:10.3969/j.issn.1671-8348.2025.12.010
阿格列汀基于Wnt/β-catenin通路调节自噬和改善肾纤维化的作用研究
Study on the effect of alogliptin in regulating autophagy and improving renal fibrosis based on the Wnt/β-catenin pathway
摘要
Abstract
Objective To explore the mechanism by which alogliptin improves renal fibrosis and its reg-ulatory effect on autophagy by inhibiting the Wnt/β-catenin pathway.Methods According to the different re-agents added,rat renal tubular epithelial cells(NRK-52E cells)were divided into different groups,and cell proliferation activity was detected using the cell counting kit-8(CCK-8);Western blot was used to detect the expression levels of transforming growth factor-β(TGF-β),α-smooth muscle actin(α-SMA),E-cadherin,au-tophagy-related proteins microtubule-associated protein 1A/1B light chain 3(LC3)-Ⅱ/Ⅰ,p62,Beclin-1 in NRK-52E cells,as well as Wnt1 and β-catenin related to the Wnt/β-catenin signaling pathway.Immunofluores-cence labeling experiments and laser confocal microscopy were used to observe the formation of autophago-somes and autolysosomes.Immunofluorescence single labeling was used to detect the expression and localiza-tion of β-catenin.Results Treatment with 50 mmol/L glucose for 72 hours and 75 mmol/L glucose for 48 hours could both inhibit the proliferative activity of NRK-52E cells.The expression levels of α-SMA and TGF-β1 in the high glucose group were increased compared with those in the normal glucose group,while the ex-pression level of E-cadherin was decreased.The differences were statistically significant(P<0.05).In the high glucose+alogliptin group,the expression levels of α-SMA and TGF-β1 decreased,and the expression level of E-cadherin increased,and the difference was statistically significant(P<0.05).The expression levels of LC3-Ⅱ/Ⅰ and Beclin-1 in the high glucose group were higher than those in the normal glucose group,while the expression level of p62 was lower.The differences were statistically significant(P<0.05).The expression level of p62 in the high glucose+alogliptin group increased,while the expression levels of LC3-Ⅱ/Ⅰ and Bec-lin-1 decreased,and the difference was statistically significant(P<0.05).Compared with the normal glucose group,the autophagic spots in the high glucose group were significantly increased and the autophagic flux was enhanced.In the high glucose+alogliptin group,autophagic spots were significantly reduced and autophagic flux was weakened.The proliferation activity of cells in the high glucose+alogliptin group and the high glu-cose+XAV939 group was enhanced,the expression level of p62 was increased,and the expression levels of Wnt1,β-catenin,LC3-Ⅱ/Ⅰ,and Beclin-1 were decreased.The differences were statistically significant(P<0.05).The proliferation activity of cells in the high glucose+alogliptin+XAV939 group was enhanced,the expression level of p62 was further increased,and the expression levels of Wnt1,β-catenin,LC3-Ⅱ/Ⅰ,and Be-clin-1 were further decreased.The differences were statistically significant(P<0.05).Compared with the high glucose group,the autophagy spots in the high glucose+lithium chloride group increased significantly.The autophagy spots in the high glucose+alogliptin+lithium chloride group were fewer than those in the former group.The autophagy spots in the high glucose+XAV939 group were significantly reduced.Conclusion Alo-gliptin improves high glucose-induced autophagic activity in NK-52 cells by inhibiting the activation of the Wnt/β-catenin signaling pathway,thereby alleviating renal fibrosis.关键词
阿格列汀/自噬/肾纤维化/Wnt/β-catenin通路Key words
alogliptin/autophagy/renal fibrosis/Wnt/β-catenin signaling pathway分类
医药卫生引用本文复制引用
RAN Yan,YANG Yuqi,PENG Yanzhe,YUAN Jing,ZHA Yan..阿格列汀基于Wnt/β-catenin通路调节自噬和改善肾纤维化的作用研究[J].重庆医学,2025,54(12):2774-2781,8.基金项目
贵州省科技计划项目(黔科合基础-ZK[2021]一般381). （黔科合基础-ZK[2021]一般381）
