年轻干细胞抗原-1阳性骨髓干细胞调控年老小鼠心脏成纤维细胞凋亡的分子机制  

Molecular mechanism of young Sca⁃1 bone marrow stem cell on old cardiac fibroblast cell apoptosis in aging mice

作　　者：吕饶 于佳迪 李柳蓁 湛楚蓝 赵立越 李月亮 董珺[2] 黎佼[1,2] LÜRao;YU Jiadi;LI Liuzhen;ZHAN Chulan;ZHAO Liyue;LI Yueliang;DONG Jun;LI Jiao(Department of Cardiology,The Sixth School of Clinical Medicine,the Affiliated Qingyuan Hospital(Qingyuan People′s Hospital),Guangzhou Medical University,Qingyuan 511518,China;Department of Geriatric,the Sec-ond Affiliated Hospital of Guangzhou Medical University,Guangzhou 510260,China;不详)

机构地区：[1]广州医科大学附属清远医院(清远市人民医院),第六临床学院,广州医科大学心脏病学系,广东清远511518 [2]广州医科大学附属第二医院老年病科,广州510260

出　　处：《实用医学杂志》2024年第17期2369-2374,共6页The Journal of Practical Medicine

基　　金：广东省基础与应用基础研究基金项目(编号:2023A1515011721,2024A1515011439);广州医科大学附属第六医院,(清远市人民医院)开放课题基金项目(编号:202201-304);广州医科大学附属第二医院临床研究项目(编号:2021-LCYJ-DZX-03,2022-LCYJ-YYDZX-03);广州医科大学2022年度学生创新能力提升计划项目(编号:广医大发[2022]66号)。

摘　　要：目的探讨Sca-1骨髓干细胞对小鼠心脏成纤维细胞(CFC)凋亡的影响,阐明年轻Sca-1骨髓干细胞调控心脏成纤维细胞凋亡的潜在分子机制及其优势。方法比较年轻与年老心脏成纤维细胞在缺氧条件下,细胞凋亡及细胞存活率。将Sca-1骨髓干细胞与年老心脏成纤维细胞共培养。通过TUNEL染色、q RT-PCR、Western Blot、CCK8试剂盒分别检测年轻或年老Sca-1骨髓干细胞对年老心脏成纤维细胞凋亡及存活的影响。通过qRT-PCR、ELISA检测年轻与年老小鼠Sca-1骨髓干细胞旁分泌生长因子并鉴定其功能。结果随年龄增加,年老小鼠心脏成纤维细胞凋亡增加,细胞存活减少。与年老细胞相比,年轻Sca-1骨髓干细胞可明显减少年老心脏成纤维细胞凋亡,增加细胞存活。机制研究发现,与年老细胞相比,年轻Sca-1骨髓干细胞可旁分泌更多的生长和分化因子5(GDF5)(P<0.05)。中和GDF5后,使年轻Sca-1骨髓干细胞失去对年老成纤维细胞凋亡及存活的调控作用。结论年轻Sca-1骨髓干细胞可通过旁分泌GDF5减少年老心脏成纤维细胞凋亡。Objective To investigate the impact of Sca-1 bone marrow derived stem cells on apoptosis in murine cardiac fibroblasts and the molecular mechanisms of young(Y)Sca-1 bone marrow stem cell(BMSC)on old(O)cardiac fibroblast cell(CFC)apoptosis.Methods The apoptosis and survival of Y and O CFC were assessed under hypoxic conditions.Co-cultures of Y and O Sca-1 bone marrow-derived mesenchymal stem cells(BMSC)with O CFC were established to investigate the impact of Sca-1 BMSC on the apoptotic response and viability of O CFC,employing TUNEL staining,qRT-PCR,Western Blot,and CCK8 assays.Furthermore,differential secretion profiles of growth factors by Y and O Sca-1 BMSC were compared using qRT-PCR and ELISA analysis.Results Compared to Y CFC,O CFC exhibited an increased rate of apoptosis and a decreased rate of cell survival.However,when compared to O cells,Y Sca-1 BMC significantly reduced apoptosis in O CFC and enhanced cell survival.Moreover,Y Sca-1 BMSC demonstrated a higher secretion of GDF5(Growth Differentiation Factor 5)than O cells(P<0.05).Importantly,the protective effects of Y Sca-1 BMSC on apoptosis and survival in O CFC were abolished upon neutral-ization of GDF5 expression.Conclusion Y Sca-1 BMSC decreases O CFC apoptosis through GDF5.

关 键 词：干细胞 心脏成纤维细胞 凋亡 细胞存活 生长因子 年轻干细胞抗原-1 

分 类 号：R363.1[医药卫生—病理学]