BM-MSCs来源外泌体介导铁死亡减轻大鼠心肌细胞系H9c2缺氧/复氧损伤

doi:10.16352/j.issn.1001-6325.2023.05.0771

基础医学与临床 ›› 2023, Vol. 43 ›› Issue (5): 771-776.doi: 10.16352/j.issn.1001-6325.2023.05.0771

BM-MSCs来源外泌体介导铁死亡减轻大鼠心肌细胞系H9c2缺氧/复氧损伤

闫霖, 陆珏秀, 罗颖, 刘先霞^*

海南医学院第二附属医院心血管内科,海南海口 570100

收稿日期:2022-11-13 修回日期:2023-03-22 出版日期:2023-05-05 发布日期:2023-04-26
通讯作者: ^*Liuxianxia2006@126.com
基金资助:
海南省社会发展项目(ZDYF2019121)

Protective effect of BM-MSCs-derived exosome-mediated ferroptosis against anoxia-reoxygenation injury in rat cardiomyoblastl cell line H9c2

YAN Lin, LU Juexiu, LUO Ying, LIU Xianxia^*

Department of Cardiovascular Medicine, the Second Affiliated Hospital of Hainan Medical University,Haikou 570100, China

Received:2022-11-13 Revised:2023-03-22 Online:2023-05-05 Published:2023-04-26
Contact: ^*Liuxianxia2006@126.com

摘要/Abstract

摘要： 目的探讨骨髓间充质干细胞(BM-MSCs)来源外泌体对大鼠心肌细胞系H9c2缺氧/复氧(A/R)损伤的保护作用及其分子机制。方法构建H9c2细胞A/R损伤模型;采用电镜、Western blot鉴定BM-MSCs来源外泌体(BM-MSCs-exos);PHK26 红色荧光标记外泌体并观察H9c2细胞内吞现象;采用CCK-8法检测细胞活力,EdU细胞增殖实验检测细胞增殖活性;铁死亡相关检测试剂盒测定Fe²⁺、丙二醛(MDA)、谷胱甘肽(GSH)含量,流式细胞测量术检测活性氧自由基(ROS)水平。结果成功鉴定BM-MSCs-exo并观察到H9c2细胞内吞外泌体;与A/R组比较,A/R+BM-MSCs-exo组细胞活力与增殖能力得到明显改善(P＜0.05);铁死亡标志蛋白GPX4、SLC7A11升高,转铁蛋白受体1(TFR1)表达降低(P＜0.05); Fe²⁺离子、MDA、ROS水平降低,GSH水平升高(P＜0.05)。铁死亡诱导剂Erastin处理后,发现BM-MSCs-exo对H9c2细胞A/R损伤的保护作用显著降低(P＜0.05)。结论 BM-MSCs-exos可减轻A/R诱导的心肌细胞系损伤,其机制可能是通过抑制心肌细胞铁死亡介导的BM-MSCs-exos。

关键词: 外泌体, 铁死亡, 心肌细胞系H9c2, 缺氧/复氧

Abstract: Objective To investigate the protective effect and molecular mechanism of bone marrow mesenchymal stem cells(BM-MSCs)-derived exosomes against anoxia-reoxygenation (A/R) injury in rat cardiomyoblast cell line H9c2. Methods The A/R injury model of H9c2 cells was constructed. Electron microscopy and Western blot were used to identify BM-MSCs-derived exosomes(BM-MSCs-exos); PHK26 red fluorescence-labeled exosomes were used to observe the endocytosis of H9c2 cells; CCK-8 assay was used to detect cell viability; EdU cell proliferation assay was used to detect cell proliferation ability; Ferroptosis-related detection kits were used to determine Fe²⁺, MDA, GSH content; Flow cytometry was used to detect reactive oxygen species free radical ROS level. Results BM-MSCs-exos were successfully identified, and the endocytosis of BM-MSCs-exos by H9c2 cells was found. Compared with A/R group, cell viability and proliferation in A/R+ MSCs-exo group were significantly improved (P＜0.05).Ferroptosis marker protein GPX4, SLC7A11 increased; Transferrin receptor TFR1 expression decreased(P＜0.05); And Fe²⁺ ions, MDA, ROS all decreased while GSH increased(P＜0.05). After treatment with the ferroptosis inducer Erastin, the protective effect of BM-MSCs-exo against A/R injury in H9c2 cells was significantly reduced (P＜0.05). Conclusions BM-MSCs-exos can alleviate A/R-induced cardiomyocyte injury, and is potentially mediated by inhibiting cardiomyocyte ferroptosis.

Key words: exosomes, ferroptosis, cardiomyoblast cell line H9c2, anoxia-reoxygenation

中图分类号:

闫霖, 陆珏秀, 罗颖, 刘先霞. BM-MSCs来源外泌体介导铁死亡减轻大鼠心肌细胞系H9c2缺氧/复氧损伤[J]. 基础医学与临床, 2023, 43(5): 771-776.

YAN Lin, LU Juexiu, LUO Ying, LIU Xianxia. Protective effect of BM-MSCs-derived exosome-mediated ferroptosis against anoxia-reoxygenation injury in rat cardiomyoblastl cell line H9c2[J]. Basic & Clinical Medicine, 2023, 43(5): 771-776.

参考文献

[1]Samsky MD, Morrow DA, Proudfoot AG, et al. Cardiogenic shock after acute myocardial infarction: a review[J]. JAMA, 2021,326:1840-1850.
[2]Wu Y, Liu H, Wang X. Cardioprotection of pharmacological postconditioning on myocardial ischemia/reperfusion injury[J]. Life Sci, 2021, 264:118-128.
[3]Hong Y, He H, Jiang G, et al. miR-155-5p inhibition rejuvenates aged mesenchymal stem cells and enhances cardioprotection following infarction[J]. Aging Cell, 2020,19:1-14.
[4]Deng S, Zhou X, Ge Z, et al. Exosomes from adipose-derived mesenchymal stem cells ameliorate cardiac damage after myocardial infarction by activating S1P/SK1/S1PR1 signaling and promoting macrophage M2 polarization[J]. Int J Biochem Cell Biol, 2019, 114:1-12.
[5]Ramesh S, Govarthanan K, Ostrovidov S, et al. Cardiac differentiation of mesenchymal stem cells: impact of biological and chemical inducers[J]. Stem Cell Rev Rep, 2021,17:1343-1361.
[6]Pegtel DM, Gould SJ. Exosomes[J]. Annu Rev Biochem, 2019, 88:487-514.
[7]Wang C, Li Z, Liu Y, et al. Exosomes in atherosclerosis: performers, bystanders, biomarkers, and therapeutic targets[J]. Theranostics, 2021, 11:3996-4010.
[8]Sahoo S, Losordo DW. Exosomes and cardiac repair after myocardial infarction[J]. Circ Res, 2014, 114:333-344.
[9]Familtseva A, Jeremic N, Tyagi SC. Exosomes: cell-created drug delivery systems[J]. Mol Cell Biochem, 2019, 459:1-6.
[10]Lin J, Li J, Huang B, et al. Exosomes: novel biomarkers for clinical diagnosis[J]. ScientificWorldJournal, 2015, 2015:657086.doi: 10.1155/2015/657086.
[11]Liu S, Chen X, Bao L, et al. Treatment of infarcted heart tissue via the capture and local delivery of circulating exosomes through antibody-conjugated magnetic nanoparticles[J]. Nat Biomed Eng, 2020, 4:1063-1075.
[12]Liu L, Jin X, Hu CF, et al. Exosomes derived from mesenchymal stem cells rescue myocardial ischaemia/reperfusion injury by inducing cardiomyocyte autophagy via AMPK and Akt pathways[J]. Cell Physiol Biochem, 2017, 43:52-68.
[13]Shen Y, Liu X, Shi J, et al. Involvement of Nrf2 in myocardial ischemia and reperfusion injury[J]. Int J Biol Macromol, 2019,125:496-502.
[14]Dixon SJ,Lemberg KM,Lamprecht MR,et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death[J].Cell, 2012, 149: 1060-1072.
[15]Stamenkovic A,Pierce GN,Ravandi A.Phospholipid oxidation products in ferroptotic myocardial cell death[J].Am J Physiol Heart Circ Physiol,2019,317: H156-H163.

BM-MSCs来源外泌体介导铁死亡减轻大鼠心肌细胞系H9c2缺氧/复氧损伤

Protective effect of BM-MSCs-derived exosome-mediated ferroptosis against anoxia-reoxygenation injury in rat cardiomyoblastl cell line H9c2

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