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【論文摘要】Direct Implantations of Erythropoietin and Autologous EPCs into Critical Limb Ischemia (CLI) Area not Only Restored the Blood Flow in CLI Area but also Rescued the Remote AMI-induced LV Dysfunction
摘要
Background/Synopsis: This study tested the hypothesis that intramuscular injections of erythropoietin (EPO) and endothelial progenitor cell (EPC) to critical limb ischemia (CLI) (i.e., primary treatment site) would also improve the heart function in rat after acute myocardial infarction (AMI) (remote ischemic organ). Objectives/Purpose: Our recent study has identified that in setting of rat acute kidney ischemia-reperfusion (KIR) (primary organ), repeated short-time intervals of bowel IR phenomenon (remote organ conditioning) could protect kidney from acute IR injury [28]. Therefore, we suppose that EPO-EPC injection to CLI area (i.e., primary treatment site) will also improve the heart function after AMI (remote organ disease) in rodent experimental model. Methods/Results: Adult-male SD rats (n=40) were equally categorized into group 1 (sham-operated control), group 2 (CLI-AMI), group 3 [CLI-AMI+EPO (10mg/kg)], group 4 [CLI-AMI+EPCs (1.2 x106)] and group 5 (CLI-AMI+EPCs+EPO). 2-D echo at day 21 and Laser doppler at day 14 showed the left-ventricular injection fraction (LVEF) and the ratio of ischemia to normal blood flow were highest in group 1, lowest in group 2, significantly higher in group 5 than in groups 3 and 4, respectively but they showed no different in later two groups (all p＜0.0001). The flow and ELISA demonstrated the circulating angiogenesis factors were significantly progressively increased from groups 1 to 5 (all p＜0.001). The number of small vessels and protein (CD31/eNOS)/cellular (vWF) expressions of the integrity of endothelial markers exhibited an identical pattern to LVEF whereas the protein (VEGF/SDF-1α)/cellular (VEGF) expressions were significantly progressively increased from groups 1 to 5 in both quadriceps/heart tissues (all p＜0.0001). The protein expressions of apoptotic (Bax/caspase-3/PARP)/inflammatory (MMP-9) and microscopic findings of ischemic/fibrotic/collagen-deposition areas and DNA-damaged marker (γ-H2AX+) were lowest in group 1and significantly progressively decreased from groups 2 to 5 in both quadriceps/heart tissues (all p＜0.0001). Conclusion: Direct injection of EPO-EPC into primary lesion of CLI not only effectively restored blood flow in CLI area but also preserved remote heart function.
延伸閱讀
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