Gene or cell therapy is currently not fully efficacious for arteriosclerosis obliterans (ASO). In this study, we determined whether YS-1402, a slow-release synthetic prostacyclin agonist, promoted neovascularization and skeletal muscle regeneration in a mouse model of critical limb ischemia (CLI). We ligated the femoral artery and its branches to obtain the CLI mouse model, administered saline (S group) or YS-1402 (YS group) to the thigh adductor 1 week after femoral artery occlusion, and evaluated tissue blood flow after surgery. After treatment, the leg muscle was obtained for histological, gene expression, and protein analyses to assess angiogenesis and skeletal muscle regeneration. Tissue blood flow improved in the YS group compared with that in the S group, and the number of CD31⁺/α-smooth muscle actin (αSMA)⁺ arterioles increased in the YS group. Prostacyclin receptor (IPR), stromal cell-derived factor-1, hepatocyte growth factor, and neural cell adhesion molecule expression levels were higher in the YS than in the S group. Skeletal muscle regeneration was detected based on PAX7- and Ki-67-positive satellite cells in the YS group. Myogenin and MyoD expression was higher in the YS than in the S group. Therefore, YS-1402 promoted functional angiogenesis and skeletal muscle regeneration in the CLI mouse model, suggesting a new therapy for ASO.

基因或细胞疗法目前对于闭塞性动脉硬化症（ASO）尚不完全有效。在这项研究中，我们确定了缓释合成前列环素激动剂YS-1402是否在关键肢体缺血（CLI）小鼠模型中促进了新血管形成和骨骼肌再生。我们将股动脉及其分支结扎以获得CLI小鼠模型，在股动脉闭塞1周后向大腿内收肌注射生理盐水（S组）或YS-1402（YS组），并评估手术后的组织血流量。治疗后，获得腿部肌肉用于组织学，基因表达和蛋白质分析，以评估血管生成和骨骼肌再生。与S组相比，YS组的组织血流量有所改善，CD31 ⁺YS组中/α平滑肌肌动蛋白（αSMA）⁺小动脉增加。YS组中前列环素受体（IPR），基质细胞衍生因子-1，肝细胞生长因子和神经细胞粘附分子的表达水平高于S组。根据YS组的PAX7和Ki-67阳性卫星细胞检测骨骼肌再生。YS中肌生成素和MyoD的表达高于S组。因此，YS-1402在CLI小鼠模型中促进了功能性血管生成和骨骼肌再生，为ASO提出了一种新疗法。