【論文摘要】Hyperbaric Oxygen Facilitates the Effect of Endothelial Progenitor Cell Therapy on Improving Outcome of Rat Critical Limb Ischemia

Pei-Lin Shao ； Hon-Kan Yip ； Shun-Cheng Wu

《海峽循環醫學雜誌》 1卷2S期 (2019/09) Pp. 131-131

https://doi.org/10.6907/SCJ.201909/SP_1(2).0105

摘要

Background/Synopsis: We tested the hypothesis that hyperbaric oxygen (HBO) (100% oxygen/2.4 atmospheres) facilitated the effect of autologous endothelial progenitor cell (EPC) therapy on restoring the blood flow in rat critical-limb ischemia (CLI). Objectives/Purpose: Adult-male-SD rats (n=8/each group) were categorized into group 1 [sham control (SC)], group 2 (CLI-treated with culture medium), group 3 [CLI-intermittent HBO (3 h/day for 5 consecutive days after CLI), group 4 (CLI-EPC/2.0 x 106 cells), and group 5 (CLI-HBO-EPC). Methods/Results: By day 5 after CLI, flow cytometry showed that the circulating EPC (Sca-1/CD31+/Ckit/ CD31+/CD34+) levels were highest in group 5 (CLI-HBO-EPC) and lowest in group 2 (CLI-treated with culture medium) (all P＜0.001). By day 14, laser Doppler demonstrated that the ratio of blood flow (i.e., CLI to normal hind-limb) was highest in group 1 [sham control (SC)] , lowest in group 2 (CLI-treated with culture medium) and significantly higher in group 5(CLI-HBO-EPC) than in groups 3 [CLI-intermittent HBO (3 h/day for 5 consecutive days after CLI) and 4(CLI-EPC/2.0 x 106 cells) (all P＜0.0001). The protein expressions of endothelial-cell biomarkers (CD31/vWF/eNOS), and numbers of endothelial-cell markers (CD31+/vWF+) and small vessels exhibited a similar pattern to blood-flow ratio among five groups, whereas the angiogenesis parameters in protein (CXCR4/SDF-1α/HIF-1α/VEGF) and cellular (HIF-1α/SDF-1α/CXCR4+) levels were progressively increased from groups 1 to 5 (all P＜0.0001). The protein expression of apoptotic (mitochondrial-Bax/cleaved-capspase-3/PARP), fibrotic (p-Smad3/TGF-ß) and mitochondrial-damaged (cytosolic-cytochrome C) exhibited an opposite pattern, whereas the protein expressions of anti-fibrotic (BMP-2/p-Smad1/5) and mitochondrial integrity (mitochondrial-cytochrome C) exhibited an identical pattern of ratio of blood flow among the five groups (all P＜0.0001). Conclusion: In, conclusion, combined HBO-EPC therapy is superior to either one alone in improving ischemia in rodent CLI.