海南医科大学学报2026，Vol.32Issue(4)：241-247,7.DOI:10.13210/j.cnki.jhmu.20250417.004
卡格列净通过抑制TXNIP信号改善肾小管上皮细胞氧化应激损伤的机制研究
Mechanism of canagliflozin on ameliorating oxidative stress injury in renal tubular epithelial cells by inhibiting TXNIP signaling
摘要
Abstract
Objective:To observe the efficacy of canagliflozin(Cana)on treating high glucose-induced oxidative stress injury in renal tubular epithelial cells HK-2 and to explore the related mechanism.Methods:The effect of Cana on the proliferation of HK-2 was detected by CCK-8 for screening the experimental safe concentration HK-2 was divided into 6 groups:the normal group(NG group),the mannitol group(MA group),the high glucose group(HG group),the Cana low-dose group,the Cana medium-dose group,and the Cana high-dose group(1,3,10 μmol/L).TXNIP,NLRP3,DRP1,MFN1,and MFN2 protein ex-pressions were detected by Western blot.Intracellular GSH-PX and SOD enzyme activities,and MDA level were examined by kit assays.The contents of inflammatory factors IL-1β and IL-18 in the cell supernatant were detected by ELISA.The level of intra-cellular mitochondrial reactive oxygen species was detected by mitoSOX Red probe,and the accumulation of DRP1 in mitochon-dria was detected by immunofluorescence.TXNIP was silenced by shRNA transfection to investigate its effects on the protein ex-pression levels of NLRP3,DRP1,MFN1,and MFN2.Results:Compared to the HG group,Cana could inhibit high glucose-induced oxidative stress and inflammatory injury,as evidenced by increased GSH-PX and SOD enzyme activity(P<0.05),reduced MDA content(P<0.05),and decreased the levels of inflammatory factors IL-1β and IL-18 in the cell supernatant(P<0.05).Cana could also inhibit the expressions of TXNIP and NLRP3 proteins(P<0.05).Additionally,while reducing the accumulation of reactive oxygen species in mitochondria,Cana could downregulate the expression of mitochondrial fission protein DRP1(P<0.05)and upregulate the expression of mitochondrial fusion proteins MFN1 and MFN2(P<0.05).After TXNIP gene silencing,the intervention effect of Cana on NLRP3,DRP1,MFN1,and MFN2 was significantly weakened.Conclusion:Cana can alleviate the oxidative stress injury of renal tubular epithelial cells induced by high glucose,and the mechanism is related to TXNIP signaling pathway.关键词
卡格列净/TXNIP/肾小管上皮细胞/氧化应激Key words
Canagliflozin/TXNIP/Renal tubular epithelial cells/Oxidative stress分类
医药卫生引用本文复制引用
周宇颖,王利,王浩..卡格列净通过抑制TXNIP信号改善肾小管上皮细胞氧化应激损伤的机制研究[J].海南医科大学学报,2026,32(4):241-247,7.基金项目
This study was supported by the Clinical Specialty of Shanghai Putuo District Health System(2021tszk02) 上海市普陀区卫生健康系统临床特色专科建设项目(2021tszk02) （2021tszk02）
