首页|高糖高脂诱发骨髓间充质干细胞损伤及铁死亡通路信号异常

高糖高脂诱发骨髓间充质干细胞损伤及铁死亡通路信号异常

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目的 探讨高糖高脂环境诱导骨髓间充质干细胞(BMSCs)损伤及其与铁死亡的相关性.方法 将BMSCs分为正常组(5.50 mmol·L-1葡萄糖)和高糖高脂组(25.00 mmol·L-1葡萄糖+0.25 mmol·L-1棕榈酸).用β-半乳糖苷酶染色评估细胞衰老情况;用酶联免疫吸附试验(ELISA)法检测肿瘤坏死因子-o(TNF-α)、白细胞介素-10(IL-10)水平;用试剂盒检测谷胱甘肽(GSH)、丙二醛(MDA)、亚铁离子(Fe2+);用蛋白质印迹法检测酰基辅酶A合成酶长链家族成员4(ACSL4)、花生四烯酸15脂氧合酶(ALOX15)、谷胱甘肽过氧化物酶4(GPX4)的蛋白表达水平.结果 正常组、高糖高脂组的细胞衰老比率分别为(6.80±1.60)%和(13.00±1.58)%,TNF-α 含量分别为(122.54±3.94)和(169.77±2.89)pg·mL-1,IL-10 含量分别为(155.16±3.97)和(105.15±7.30)pg·mL-1,GSH 含量分别为 4.30±0.33 和 1.55±0.14,MDA含量分别为2.94±0.10和5.84±0.10,Fe2+含量分别为6.22±0.35和16.13±0.36,ACSL4蛋白相对表达水平分别为0.42±0.05和0.84±0.10,ALOX15蛋白相对表达水平分别为0.61±0.25和1.06±0.11,GPX4蛋白相对表达水平分别为1.13±0.17和0.33±0.08.高糖高脂组的上述指标与正常组比较,在统计学上差异均有统计学意义(均P<0.01).结论 高糖高脂诱导BM-SCs的损伤,在这一过程中铁死亡扮演了重要角色.
High glucose and high fat can induce bone marrow mesenchymal stem cells damage and abnormal ferroptosis signaling pathway
Objective To investigate the relationship between the injury and ferroptosis of bone marrow mesenchymal stem cells(BMSCs)induced by high glucose and high fat.Methods BMSCs were divided into normal group(5.50 mmol·L-1 glucose)and high glucose and high fat(HGHF)group(25.00 mmol·L-1 glucose+0.25 mmol·L-1 palmitic acid).Assessment of cellular aging via β-galactosidase staining;enzyme linked immunosorbent assay(ELISA)were used to detect tumor necrosis factor-α(TNF-α),interleukin-10(IL-10)release levels;glutathione(GSH),malondialdehyde(MDA)and ferrous ion(Fe2+)detection kits were used to detect ferroptosis related indicators;Western blotting was used to detect the expression of ferroptosis related signaling pathway protein acyl-CoA synthetase long chain family member 4(ACS14)/arachidonate 15-lipoxygenase(ALOX15)/glutathione peroxidase 4(GPX4).Results The senescence rates of normal group HGHF group were(6.80±1.60)%and(13.00±1.58)%;the levels of TNF-α were(122.54±3.94)and(169.77±2.89)pg·mL-1;the levels of IL-10 were(155.16±3.97)and(105.15±7.30)pg·mL-1;GSH levels were 4.30±0.33 and 1.55±0.14;MDA levels were 2.94±0.10 and 5.84±0.10;Fe2+levels were 6.22±0.35 and 16.13±0.36;the relative expression levels of ACSL4 protein were 0.42±0.05 and 0.84±0.10;the relative ALOX15 protein were 0.61±0.25 and 1.06±0.11;the relative expression levels of GPX4 protein were 1.13±0.17 and 0.33±0.08,respectively.The above indexes in the HGHF group were significantly different from those in the normal group(all P<0.05).Conclusion 25 mmol·L-1 glucose combined with 0.25 mmol·L-1 palmitic acid for 24 h can be used as a suitable condition to induce BMSCs injury.ferroptosis plays an important role in BMSCs injury induced by high glucose and high fat.

high glucose and high fatbone marrow mesenchymal stem cellsferroptosis

阿布都拉·米热合买提、祖丽胡马·热合曼、李包娟、叶雨萌、张䶮之

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新疆医科大学药学院,新疆维吾尔自治区乌鲁木齐 830011

新疆天然药物活性组分与释药技术重点实验室,新疆维吾尔自治区乌鲁木齐 830011

高糖高脂 骨髓间充质干细胞 铁死亡

国家自然科学基金资助项目新疆天然药物活性组分与释药技术重点实验室基金资助项目

81760767XJDX1713

2024

中国临床药理学杂志
中国药学会

中国临床药理学杂志

CSTPCD北大核心
影响因子:1.91
ISSN:1001-6821
年,卷(期):2024.40(17)