尿石素A调控线粒体自噬及衰老信号通路拮抗糖尿病环境诱导的骨髓间充质干细胞异常

doi:10.7506/spkx1002-6630-20250327-203

食品科学 ›› 2025, Vol. 46 ›› Issue (19): 185-194.doi: 10.7506/spkx1002-6630-20250327-203

• 营养卫生 • 上一篇

尿石素A调控线粒体自噬及衰老信号通路拮抗糖尿病环境诱导的骨髓间充质干细胞异常

张䶮之，周克春，李包娟，王若彤，阿不都拉·米热合买提

（1.新疆医科大学药学院，新疆乌鲁木齐 830000；2.新疆天然药物活性组分与释药技术重点实验室，新疆乌鲁木齐 830000）

发布日期:2025-09-16
基金资助:
新疆天然药物活性组分与释药技术重点实验室开放课题（2024XJTRZ03）；国家自然科学基金地区科学基金项目（82560727）；新疆地区高发疾病研究教育部重点实验室开放课题（2024A02）

Urolithin A Regulates Mitophagy and Senescence Signaling Pathways to Antagonize Diabetic Environment-Induced Abnormalities in Bone Marrow Mesenchymal Stem Cells

ZHANG Yanzhi, ZHOU Kechun, LI Baojuan, WANG Ruotong, ABUDOULA·Mirehemaiti

(1. College of Pharmacy, Xinjiang Medical University, ürümqi 830000, China; 2. Key Laboratory of Xinjiang Active Components of Natural Medicines and Drug Release Technology, ürümqi 830000, China)

Published:2025-09-16

摘要/Abstract

摘要： 目的：探究石榴活性产物尿石素A（urolithin A，UA）对糖尿病模拟环境下骨髓间充质干细胞（bone marrow mesenchymal stem cells，BMSC）线粒体自噬及衰老的影响并初步探讨信号机制。方法：分离、培养与鉴定C57小鼠BMSC，使用30 mmol/L葡萄糖和0.5 mmol/L棕榈酸构建细胞衰老模型，使用不同质量浓度UA干预，CCK-8法检测细胞活力，β-半乳糖苷酶染色法检测细胞衰老率，DCFH-DA和Mito SOX荧光探针检测活性氧（reactive oxygen species，ROS）水平，流式细胞术检测凋亡率，Western Blot检测衰老和线粒体自噬相关蛋白表达水平。结果：提取的小鼠BMSC Sca-1、CD29阳性表达，CD45、CD11b阴性表达，30 mmol/L葡萄糖＋0.5 mmol/L棕榈酸干预48 h为最佳造模条件，UA干预后细胞活力增加，细胞凋亡明显减少，β-半乳糖苷酶染色阳性细胞率减少，细胞及线粒体ROS荧光强度降低，张力蛋白同源物诱导的蛋白激酶1（PTEN induced putative kinase 1，PINK1）、自噬受体蛋白P62表达显著降低，Parkin E3泛素-蛋白连接酶（Parkin E3 ubiquitin protein ligase，PARKIN）、微管相关蛋白轻链3（microtubule-associated protein light chain 3，LC3）表达显著升高，并呈剂量依赖性。细胞核中核因子-红细胞2相关因子2（nuclear factor erythroid 2-related factor 2，NRF2）蛋白表达显著降低，沉默信息调节因子1（sirtuin 1，SIRT1）、肿瘤蛋白53（tumor protein 53，P53）蛋白表达显著升高，胞浆中NRF2蛋白表达显著升高，SIRT1、P53蛋白表达显著降低，并呈剂量依赖性。结论：UA抑制糖尿病高糖高脂环境引发的BMSC线粒体自噬障碍，减少BMSC衰老，其机制可能是通过激活PINK1/PARKIN线粒体自噬，并可能通过调控NRF2/SIRT1/P53衰老信号恢复干细胞质量。

关键词: 尿石素A；高糖高脂；骨髓间充质干细胞；衰老；自噬

Abstract: Objective: To explore the effect of urolithin A (UA), a bioactive compound from pomegranate, on mitophagy and aging in bone marrow mesenchymal stem cells (BMSC) in a simulated diabetic environment and to elucidate the underlying signaling mechanism. Methods: BMSC were isolated, cultured and identified from C57 mice. Cellular senescence was induced by exposing BMSC to 30 mmol/L glucose and 0.5 mmol/L palmitic acid. The senescence cells were then treated with UA at different mass concentrations. Cell viability was detected by the Counting Kit-8 (CCK-8) assay, senescent cells were detected by β-galactosidase staining, reactive oxygen species (ROS) levels were detected using the fluorescent probes 2’,7’-dichlorofluorescin-diacetate (DCFH-DA) and Mito SOX, and the expression levels of proteins related to aging and mitochondrial autophagy were detected by Western Blot. Results: BMSCs showed positive expression of Sca-1 and CD29, and negative expression of CD45 and CD11b. The optimal conditions for inducing cellular senescence were 48 h exposure to 30 mmol/L glucose plus 0.5 mmol/L palmitic acid. Following UA intervention, cell viability increased; cell apoptosis, the rate of galactosidase positive cells, and fluorescence intensities for cellular and mitochondrial ROS decreased. In addition, PTEN induced putative kinase 1 (PINK1) and P62 expression significantly decreased, whereas the expression of Parkin E3 ubiquitin protein ligase (PARKIN) and microtubule-associated protein light chain 3 (LC3) significantly increased. The protein expression of nuclear factor erythroid 2-related factor 2 (NRF2) in the nucleus significantly dropped, while the protein expression of sirtuin 1 (SIRT1) and tumor protein 53 (P53) significantly increased. Meanwhile, the opposite results were observed in the cytoplasm. All the above effects were dose-dependent. Conclusion: UA could inhibit diabetes-induced mitophagy disorder and reduce senescence in BMSC. The underlying mechanisms may involve activation of the PINK1/Parkin mitophagy pathway and regulation of the NRF2/SIRT1/P53 senescence signaling axis, potentially restoring stem cell quality.

Key words: urolithin A; high glucose and palmitic acid; bone marrow mesenchymal stem cells; aging; autophagy

中图分类号:

R965

张䶮之，周克春，李包娟，王若彤，阿不都拉·米热合买提. 尿石素A调控线粒体自噬及衰老信号通路拮抗糖尿病环境诱导的骨髓间充质干细胞异常[J]. 食品科学, 2025, 46(19): 185-194.

ZHANG Yanzhi, ZHOU Kechun, LI Baojuan, WANG Ruotong, ABUDOULA·Mirehemaiti. Urolithin A Regulates Mitophagy and Senescence Signaling Pathways to Antagonize Diabetic Environment-Induced Abnormalities in Bone Marrow Mesenchymal Stem Cells[J]. FOOD SCIENCE, 2025, 46(19): 185-194.

[1]	胡晓彤安丽萍. 桑黄子实体多糖的提取及其对D-gal诱导的3T3细胞损伤的保护作用[J]. , 0, (): 0-0.
[2]	冯晴霞，闫宇宁，杨峄，周嘉宁，李乐斌，卢学春，安丽萍. 姬松茸多肽提取物对D-半乳糖致衰老模型小鼠的保护作用[J]. 食品科学, 2020, 41(7): 164-170.
[3]	冯晴霞. 姬松茸多肽提取物对D-半乳糖致衰老模型小鼠的保护作用[J]. 食品科学, 0, (): 0-0.
[4]	牛真真郭遥遥赵新玲金宏公衍玲. 谷胱甘肽对小鼠的抗疲劳作用及其机制的研究[J]. 食品科学, 0, (): 0-0.
[5]	王妙颖，阿依姑丽·艾合麦提，曹梦丽，艾力牙尔·吾不力. 柠檬酸对高脂血症小鼠胰岛素敏感性的影响[J]. 食品科学, 2019, 40(9): 132-138.
[6]	王妙颖阿依姑丽·艾合麦提曹梦丽艾力牙尔·吾不力. 柠檬酸对高脂血症小鼠胰岛素敏感性的影响[J]. 食品科学, 0, (): 0-0.
[7]	闵佳玲，许春莲，舒翔，邱奇琦，聂少平，谢明勇，胡晓鹃. 长期槲皮素膳食暴露对小鼠乳腺发育的影响[J]. 食品科学, 2018, 39(21): 116-121.
[8]	阿依姑丽·艾合麦提，王妙颖，彭禛菲，冯雅丽，王小燕，古扎丽努尔·艾尼. 野山杏果肉总有机酸对高脂血症大鼠血脂及相关基因表达的影响[J]. 食品科学, 2018, 39(21): 171-176.
[9]	闵佳玲许春莲舒翔邱奇琦聂少平谢明勇胡晓鹃. 长期槲皮素膳食暴露对于小鼠乳腺发育的影响[J]. 食品科学, 0, (): 0-0.
[10]	阮海华，胡双艳，张春晨，曹婳，张真. 单宁酸通过抑制TRAF6向细胞质膜的招募抑制Akt信号通路[J]. 食品科学, 2018, 39(7): 188-194.
[11]	阮海华胡双艳张真. 单宁酸通过抑制TRAF6向细胞质膜的招募抑制Akt信号通路[J]. 食品科学, 0, (): 0-0.
[12]	阮海华胡双艳张真. 单宁酸通过抑制表皮生长因子受体特异位点的磷酸化诱导细胞凋亡[J]. 食品科学, 0, (): 0-0.
[13]	阮海华，胡双艳，张春晨，余龙，张真. 单宁酸通过选择性抑制表皮生长因子受体特定位点磷酸化抑制肿瘤细胞的增殖[J]. 食品科学, 2018, 39(5): 199-205.
[14]	司茹郑梦思邹莉波. 美藤果油辅助改善小鼠记忆的功效研究[J]. 食品科学, 0, (): 0-0.
[15]	司茹，郑梦思，邹莉波. 美藤果油辅助改善小鼠记忆的功效[J]. 食品科学, 2017, 38(9): 202-206.

尿石素A调控线粒体自噬及衰老信号通路拮抗糖尿病环境诱导的骨髓间充质干细胞异常

Urolithin A Regulates Mitophagy and Senescence Signaling Pathways to Antagonize Diabetic Environment-Induced Abnormalities in Bone Marrow Mesenchymal Stem Cells

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价