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目的 探讨骨髓间充质干细胞(BMSCs)对转化生长因子(TGF)-β1诱导的肾小管上皮细胞损伤的保护作用。方法 体外培养大鼠BMSCs和肾小管上皮细胞(HK-2),将HK-2细胞分为对照组、模型组(TGF-β1 5 ng/ml)、治疗组(TGF-β1 5 ng/ml+BMSCs)、抑制组[TGF-β1 5 ng/ml+BMSCs+10μmol/L糖原合成酶激酶(GSK)3β抑制剂SB216763]。线粒体膜电位(MMP)检测试剂盒测定细胞MMP,三磷酸腺苷(ATP)测定试剂盒测量细胞ATP含量，酶联免疫吸附试验检测各组细胞白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α、IL-1β水平，实时荧光定量聚合酶链反应(qRT-PCR)检测HK-2细胞中E-钙黏蛋白(cadherin)、α-平滑肌肌动蛋白(SMA)、抗纤连蛋白(FN)、微管相关蛋白1轻链3(LC3)Ⅱ、LC3Ⅰ、Sma和Mad相关蛋白(SMAD)3、沉默调节蛋白(SIRT)1、GSK3β mRNA表达，Western印迹检测E-cadherin、α-SMA、FN、LC3Ⅱ、LC3Ⅰ、SMAD3、SIRT1、GSK3β及谷胱甘肽过氧化物酶(GPX)4蛋白表达，免疫荧光检测GPX4蛋白表达。结果 与对照组比较，模型组中E-cadherin mRNA和蛋白表达均明显降低，LC3Ⅱ、LC3Ⅰ、α-SMA、FN、GSK3β、SMAD3 mRNA和蛋白表达明显降低，GPX4蛋白表达明显降低，IL-6、TNF-α、IL-1β水平均明显提高，JC-1红/绿荧光比值和ATP含量明显下降(P<0.05);与模型组比较，治疗组可显著提高E-cadherin、SIRT1 mRNA和蛋白表达，明显降低LC3Ⅱ、LC3Ⅰ、α-SMA、FN、GSK3β、SMAD3 mRNA和蛋白表达，明显升高GPX4蛋白表达，明显降低IL-6、TNF-α、IL-1β水平，明显提高JC-1红/绿荧光比值和ATP含量(P<0.05);与治疗组比较，添加GSK3β抑制剂可显著降低GSK3β、SMAD3 mRNA和蛋白表达，明显提高SIRT1 mRNA和蛋白表达(P<0.05)。结论 BMSCs可通过调控GSK3β介导TGF-β1/SMAD3信号传导抑制肾小管上皮间质转化(EMT)过程而发挥抗肾脏纤维化作用，BMSCs还可通过调控GSK3β介导线粒体自噬抑制炎症反应和铁死亡而发挥肾保护作用。
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基本信息:
中图分类号:R692
引用信息:
[1]孙源博,李悦,施展,等.基于GSK3β探讨骨髓间充质干细胞对TGF-β1诱导的肾小管上皮细胞损伤的保护作用[J].中国老年学杂志,2026,46(10):1849-1854.
基金信息:
黑龙江省教育厅青年创新人才项目(UNPYSCT-2018120);黑龙江省教育厅基本科研业务费(支持计划)(2020-KYYWF-0773); 2024年牡丹江医学院附属红旗医院博士科研启动基金(2024-HQBS-08); 2019年度黑龙江省省属高等学校基本科研业务费科研项目(2019-KYYWFMY-0047)
2026-05-22
2026-05-22