Hypoxic preconditioning attenuates hypoxia/reoxygenation-induced apoptosis in mesenchymal stem cells
Hypoxic preconditioning attenuates hypoxia/reoxygenation-induced apoptosis in mesenchymal stem cells
复制标题
缺氧预处理减轻缺氧/复氧诱导的间充质干细胞凋亡
DOI：
10.1111/j.1745-7254.2008.00716.x
复制
发表时间：
2008-01-01
影响因子：
8.2
通讯作者：
Zhang, Xing
中科院分区：
文献类型：
--
作者：
Wang, Jian-an;Chen, Tie-long;Zhang, Xing
摘要目的：间充质干细胞（MSC）是心脏替代疗法的一个有前途的候选细胞。然而，大多数移植的MSC在移植后由于血液供应不良、缺血-再灌注和炎症因子而容易丢失。目的：研究缺氧预处理（hypoxia preconditioning，HPC）对缺氧/复氧诱导的MSC凋亡的影响。方法：将3代MSC分为6组，即正常组、缺氧/复氧（hypoxia/reoxygenation，H/R）组、环孢素A（cyclosporine A，CsA）组、HPC 10 min、20 min、30 min组。结果：HPC可降低H/R诱导的细胞凋亡指数，提高H/R诱导的细胞存活率，并可降低H/R诱导的细胞凋亡指数，增加细胞存活率，同时检测细胞线粒体膜电位、细胞外调节激酶（ERK）、Akt、缺氧诱导因子1-α（HIF 1-α）和血管内皮生长因子（VEGF）的表达。HPC能显著稳定线粒体膜电位，上调Bcl-2和VEGF的表达，增加ERK和Akt的磷酸化。结论：HPC通过稳定线粒体膜电位、上调Bcl-2和VEGF表达、促进ERK和Akt磷酸化，对H/R诱导的MSC凋亡具有保护作用。HPC对开发新的干细胞保护策略具有重要意义。
AbstractAim:Mesenchymal stem cells (MSC) are a promising candidate for cardiac replacement therapies. However, the majority of transplanted MSC are readily lost after transplantation because of poor blood supply, ischemia-reperfusion, and inflammatory factors. We aimed to study the effects of hypoxia preconditioning (HPC) on hypoxia/reoxygenation-induced apoptosis of MSC.Methods:Three generations of MSC were divided into 6 groups, including the normal group, hypoxia-reoxygenation (H/R) group, cyclosporine A (CsA), and the HPC 10 min, 20 min, and 30 min groups. The apoptotic index, cell viability, mitochondrial membrane potential, translocation of Bcl-2 and bax, extracellular regulated kinase (ERK), Akt, hypoxia-inducible factor 1-α, and the vascular endothelial growth factor (VEGF) were tested after H/R treatment.Results:HPC decreased the apoptotic index and increased the viability induced by H/R. Moreover, HPC markedly stabilized mitochondrial membrane potential, upregulated Bcl-2 and VEGF expressions, and increased the phosphorylation of ERK and Akt. As a positive control, CsA has the same function as HPC, except for promoting ERK and Akt phosphorylation and upregulating VEGF.Conclusion:HPC had a protective effect against MSC apoptosis induced by H/R via stabilizing mitochondrial membrane potential, upregulating Bcl-2 and VEGF, and promoting ERK and Akt phosphorylation. HPC has implications for the development of novel stem cell protective strategies.