[1]续斌,杨燕,高健,等.黄芩素调控SLC7A11/GPX4信号通路改善铁死亡促进骨髓间充质干细胞成骨分化实验研究[J].陕西医学杂志,2026,(6):761-768.[doi:DOI:10.3969/j.issn.1000-7377.2026.06.007]
　XU Bin,YANG Yan,GAO Jian,et al.Baicalein regulating SLC7A11/GPX4 signaling pathway to improve ferroptosis and promote osteogenic differentiation of BMSCs[J].,2026,(6):761-768.[doi:DOI:10.3969/j.issn.1000-7377.2026.06.007]
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黄芩素调控SLC7A11/GPX4信号通路改善铁死亡促进骨髓间充质干细胞成骨分化实验研究

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2026年6期
页码:
761-768
栏目:
基础研究
出版日期:
2026-06-05

文章信息/Info

Title:
Baicalein regulating SLC7A11/GPX4 signaling pathway to improve ferroptosis and promote osteogenic differentiation of BMSCs
作者:
续斌; 杨燕; 高健; 柴浩; 王国胜
（新疆医科大学第六附属医院创伤二科，新疆 乌鲁木齐 830000）
Author(s):
XU Bin; YANG Yan; GAO Jian; CHAI Hao; WANG Guosheng
(The Second Department of Trauma,Sixth Affiliated Hospital of Xinjiang Medical University,Urumqi 830000,China)
关键词:
骨质疏松; 骨髓间充质干细胞; 黄芩素; 铁死亡; 溶质载体家族7成员11/谷胱甘肽过氧化物酶4通路; 成骨分化
Keywords:
Osteoporosis; Bone marrow mesenchymal stem cells; Baicalein; Ferroptosis; SLC7A11/GPX4 pathway; Osteogenic differentiation
分类号:
R 285.5
DOI:
DOI:10.3969/j.issn.1000-7377.2026.06.007
文献标志码:
A
摘要:
目的：探讨黄芩素（BAI）通过调控溶质载体家族 7 成员11（SLC7A11）/谷胱甘肽过氧化物酶4（GPX4）信号通路抑制骨髓间充质干细胞（BMSCs）铁死亡、促进成骨分化的作用。方法：采用高糖高脂（HGHF）环境联合铁死亡诱导剂 Erastin 构建BMSCs铁死亡及成骨功能受损模型，并给予BAI及铁死亡抑制剂 Ferrostatin-1（Fer-1）干预。实验分为五组：①对照组（正常培养条件）；②模型组（HGHF环境）；③铁死亡诱导剂组（HGHF+300 μmol/L Erastin）；④模型+BAI组（HGHF+20 μmol/L BAI）；⑤模型+铁死亡抑制剂组（HGHF+10 μmol/L Fer-1）。采用CCK-8法检测细胞活力；采用透射电镜观察线粒体超微结构变化；应用二氯荧光素（DCFH-DA）探针及相关试剂盒检测活性氧（ROS）、丙二醛（MDA）、谷胱甘肽（GSH）水平；采用茜素红S染色评价矿化结节形成；采用Western blot法检测SLC7A11、GPX4、酰基辅酶A合成酶长链家族成员4（ACSL4）、铁蛋白重链1（FTH1）及成骨相关蛋白Runt相关转录因子2（RUNX2）、Ⅰ型胶原α1链（COL1A1）、骨钙素（OCN）的表达水平。结果：与对照组比较，模型组和铁死亡诱导剂组的BMSCs细胞活力显著降低，线粒体结构出现明显萎缩、膜破裂和嵴减少（均P＜0.05）。与模型组和铁死亡诱导剂组比较，模型+BAI组细胞活力明显提高，线粒体结构得到显著改善，细胞内ROS、MDA水平显著降低，GSH水平显著升高（均P＜0.05）。同时，BAI干预显著上调SLC7A11、GPX4、FTH1、RUNX2、COL1A1和OCN的蛋白表达，显著下调ACSL4的表达，促进矿化结节的形成（均P＜0.05）。这些结果表明，BAI能够有效改善BMSCs的活性和成骨分化能力，其效果与模型+铁死亡抑制剂组相似。结论：BAI可通过激活SLC7A11/GPX4信号通路抑制BMSCs铁死亡，减轻氧化应激损伤，从而恢复其成骨分化能力。
Abstract:
Objective:To investigate the role of Baicalein (BAI) in inhibiting ferroptosis in bone marrow mesenchymal stem cells (BMSCs) and promoting osteogenic differentiation through regulating the solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway.Methods：A BMSCs ferroptosis and osteogenic dysfunction model was established by using a high-fat,high-glucose (HGHF) environment combined with the ferroptosis inducer Erastin,followed by intervention with BAI and ferroptosis inhibitor Ferrostatin-1 (Fer-1).The experiment was divided into five groups:①Control group (normal culture conditions);②Model group (HGHF environment);③Ferroptosis inducer group (HGHF+300 μmol/L Erastin);④Model+BAI group (HGHF+20 μmol/L BAI);⑤Model+ferroptosis inhibitor group (HGHF+10 μmol/L Fer-1).Cell viability was measured using the CCK-8 assay.Mitochondrial ultrastructure was observed by transmission electron microscopy.Reactive oxygen species (ROS),malondialdehyde (MDA),and glutathione (GSH) levels were assessed using DCFH-DA probes and related kits.Mineralized nodule formation was evaluated by alizarin red S staining;and the expression levels of SLC7A11,GPX4,acyl-CoA synthetase long-chain family member 4 (ACSL4),ferritin heavy chain 1 (FTH1),and osteogenic markers runt-related transcription factor 2 (RUNX2),collagen type Ⅰ alpha 1 chain (COL1A1),and osteocalcin (OCN) were measured by Western blot.Results:Compared with the control group,the BMSCs cell viability in the model group and ferroptosis inducer group was significantly decreased,with obvious mitochondrial shrinkage,membrane rupture,and cristae reduction (all P<0.05).Compared with the model group and the ferroptosis inducer group,the cell viability of the model+BAI group was significantly enhanced,the mitochondrial structure was significantly improved,the intracellular ROS and MDA levels were significantly decreased,and the GSH level was significantly increased (all P<0.05).Meanwhile,BAI intervention significantly upregulated the protein expressions of SLC7A11,GPX4,FTH1,RUNX2,COL1A1 and OCN,significantly downregulated the expression of ACSL4,and promoted the formation of mineralized nodules (all P<0.05).These results indicated that BAI could effectively enhance the activity and osteogenic differentiation ability of BMSCs,and its effect was similar to that of the model+ferroptosis inhibitor group.Conclusion:BAI can inhibit ferroptosis in BMSCs and alleviate oxidative stress injury by activating the SLC7A11/GPX4 signaling pathway,thereby restoring their osteogenic differentiation ability.

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备注/Memo

备注/Memo:
新疆维吾尔自治区自然科学基金资助项目（2019D01C246）；新疆维吾尔自治区“天山英才”医药卫生高层次人才培养计划(TSYC202301B107)
更新日期/Last Update: 2026-06-05