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Combined treatment with erythropoietin and granulocyte colony-stimulating factor enhances neovascularization and improves cardiac function after myocardial infarction

引用

Chinese Medical Journal 2014年第9期127卷 1677-1683页

作者： Xue Jingyi Du Guoqing Shi Jing Li Yue Masahiro Yasutake Liu Lei Li Jianqiang Kong Yihui Wang Shuxian Yun Fengxiang Li Weimin Department of Cardiology the First Clinical Hospital Harbin Medical University Harbin Heilongjiang 150001 China Department of Ultrasound the Second Clinical Hospital HarbinMedical University Harbin Heilongjiang 150086 China Department of Cardiovascular Medicine Nippon Medical SchoolTokyo Japan

Background Erythropoietin （EPO） and granulocyte colony-stimulating factor （G-CSF） are both potential novel therapeutics for use after myocardial infarction （MI）.However,their underlying mechanisms remain unclear and the efficacy of monotherapy with EPO or G-CSF is also ***,we investigated the effects of combined treatment with EPO and G-CSF on neovascularization and cardiac function in post-infarction rats and explored the potential *** Four groups of rats were used：control （saline injection after MI,i.h.）,EPO （a single dose of 5 000 IU/kg after MI,i.h.）,G-CSF （a dose of 50 μg· kg-1· d-1 for 5 days after MI,i.h.）,and both EPO and G-CSF （EPO＋G-CSF,using the same regiment as above）.Cardiac function was assessed by echocardiography before and 1 day,7 days,14 days and 21 days after ***34＋/Flk-1＋ cells in the peripheral blood were evaluated by flow cytometry before and 3 days,5 days and 7 days after *** infarct area and angiogenesis in the peri-infarct area were *** mRNA and protein expression of vascular endothelial growth factor （VEGF） and stromal-derived factor-1α （SDF-1α） in the peri-infarct area were detected by real-time quantitative RT-PCR and Western *** Compared with the control and monotherapy groups,the EPO＋G-CSF group had significantly increased CD34＋/ Flk-1＋ endothelial progenitor calls （EPCs）in the peripheral blood （P ＜0.05）,up-regulated VEGF and SDF-1α levels in the peri-infarct region （P ＜0.05）,enhanced capillary density （P ＜0.05）,reduced infarct size （P ＜0.05） and improved cardiac structure and function （P ＜0.05）.G-CSF alone did not dramatically increase EPCs in the peripheral blood,enhance capillary density in the peri-infarct area or reduce infarct size compared with the control *** Combined treatment with EPO and G-CSF increased EPCs mobilization,up-regulated VEGF and SDF-1α levels in the post-infarction microenvironment,subsequently enhanced neovascularization in the peri-inf

关键词： erythropoietin granulocyte colony-stimulating factor acute myocardial infarction endothelial progenitor cells mobilization neovascularization

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