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首页> 外文期刊>Cellular Physiology and Biochemistry >Hydrogen Sulfide-Preconditioning of Human Endothelial Progenitor Cells Transplantation Improves Re-Endothelialization in Nude Mice with Carotid Artery Injury
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Hydrogen Sulfide-Preconditioning of Human Endothelial Progenitor Cells Transplantation Improves Re-Endothelialization in Nude Mice with Carotid Artery Injury

机译:硫化氢预处理人内皮祖细胞移植可改善颈动脉损伤裸鼠的再内皮化。

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>Background/Aims: The aim of present study was to test the hypothesis that preconditioning with sodium hydrosulfide (NaHS) could enhance the capacity of migration, adhesion and proliferation of endothelial progenitor cells (EPCs) in vitro, and also could improve the efficacy of EPCs transplantation for re-endothelialization in nude mice with carotid artery injury. The paper further addressed the underlying mechanisms. Methods: EPCs were isolated from peripheral blood mononuclear cells of healthy male volunteers and the markers of EPCs were analyzed by flow cytometry. Thereafter, different concentrations of NaHS (25, 50, 100, 200 and 500 uM) were used for preconditioning EPCs. In vitro and in vivo migration, adhesion and proliferation as well as nitric oxide (NO) production of EPCs were evaluated. Carotid artery injury model was produced in nude mice and thereafter, NaHS-preconditioned EPCs were transplanted in order to evaluate their capacity of re-endothelialization. Results: Cellular immuno-staining showed that isolated cells expressed the key markers of EPCs. In vitro, EPCs proliferation rates and NO production were gradually increased in a NaHS-concentration dependent manner, while these benefits were blocked at a concentration of 500 uM NaHS. Similarly, the migration and adhesion rates of EPCs were also increased the most prominently at a concentration of 200 ?μM NaHS. In vivo, compared to the control group, treatment with NaHS-preconditioned EPCs significantly enhanced the capacity of re-endothelialization of EPCs. Fluorescent microscope revealed that there were more EPCs homing to the injury vessels in the NaHS-preconditioned EPCs group than the non-preconditioned group. With the administration of AMPK or eNOS inhibitors respectively, the above benefits of NaHS-preconditioning were abrogated. Conclusion: These results suggested that NaHS-preconditioning enhanced the biological function and re-endothelialization of EPCs through the AMPK/eNOS signaling pathway.
机译:> 背景/目的: 本研究的目的是检验以下假设:使用硫化氢钠(NaHS)进行预处理可以增强动物的迁移,粘附和增殖能力。内皮祖细胞(EPCs)的体外实验,也可以提高颈动脉损伤裸鼠的内皮祖细胞移植再内皮化的功效。该文件进一步探讨了潜在的机制。 方法: 从健康男性志愿者的外周血单个核细胞中分离EPC,并通过流式细胞仪分析EPC的标记。此后,将不同浓度的NaHS(25、50、100、200和500 uM)用于预处理EPC。评估了EPC的体外和体内迁移,粘附和增殖以及一氧化氮(NO)的产生。在裸鼠中建立颈动脉损伤模型,然后移植经过NaHS预处理的EPC,以评估其再内皮化的能力。 结果: 细胞免疫染色表明,分离的细胞表达了EPC的关键标记。 体外,EPC的增殖速率和NO的产生以NaHS浓度依赖性方式逐渐增加,而在500 uM NaHS的浓度下这些益处却被阻止。同样,在浓度为200 µμM NaHS的情况下,EPC的迁移和粘附速率也最明显地增加。 体内与对照组相比,用NaHS预处理的EPC治疗显着增强了EPC的再内皮化能力。荧光显微镜显示,在经过NaHS预处理的EPCs组中,归巢于损伤血管的EPC数量多于未经过预处理的EPC。分别施用AMPK或eNOS抑制剂后,NaHS预处理的上述好处被废除了。 结论: 这些结果表明,NaHS预处理通过AMPK / eNOS信号通路增强了EPC的生物学功能和重新内皮化。

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