Huang Jing-Juan, Shi Yi-Qin, Li Rui-Lin, Hu An, Zhou Hong-Sheng, Cheng Qian, Xu Zheng, Yang Zhi-Ming, Hao Chang-Ning, Duan Jun-Li
Department of Gerontology, Xin Hua Hospital, Shanghai Jiaotong University School of Medicine Kongjiang Road 1665, Shanghai 200092, China.
Department of Vascular Surgery, Ren Ji Hospital, Shanghai Jiaotong University School of Medicine Dongfang Road 1630, Shanghai 200127, China.
Am J Transl Res. 2014 Nov 22;6(6):703-13. eCollection 2014.
Although significant progress in bypass surgery and catheter intervention against peripheral artery disease, the number of severe critical limb ischemia (CLI) patients is increasing. Thus, it is crucial to develop new, non-invasive therapeutic strategies. The purpose of this study was to determine the mechanism of therapeutic ultrasound (TUS) on ischemic angiogenesis using mouse model of hindlimb ischemia and the cellular/molecular mechanisms underlying TUS-related neovascularization. The hindlimb ischemic mice were exposed to extracorporeal TUS for 3, 6, 9 minute per day (1 MHz, 0.3 W/cm(2)) until day 14 after left femoral artery ligation. Increased blood perfusion and capillary density were determined following 9 min of TUS compared with ischemic group. Moreover, TUS treatment increased the protein levels of vascular endothelial growth factor (VEGF), hypoxic inducible factor-1α (HIF-1α), endothelial nitric oxide synthase (eNOS) and p-Akt in vivo. TUS promoted capillary-like tube formation, migration and motility of human umbilical venous endothelial cells (HUVECs). Furthermore, the protein expressions of VEGF, eNOS and p-Akt were increased after TUS treatment. In conclusion, TUS therapy promotes postnatal neovascularization through multiple angiogenic pathways in mice model of ischemic hindlimb.
尽管在针对外周动脉疾病的搭桥手术和导管介入治疗方面取得了显著进展，但严重肢体缺血（CLI）患者的数量仍在增加。因此，开发新的非侵入性治疗策略至关重要。本研究的目的是利用后肢缺血小鼠模型确定治疗性超声（TUS）对缺血性血管生成的作用机制以及TUS相关新生血管形成的细胞/分子机制。将后肢缺血小鼠每天暴露于体外TUS 3、6、9分钟（1兆赫，0.3瓦/平方厘米），直至左股动脉结扎后第14天。与缺血组相比，TUS照射9分钟后测定血液灌注增加和毛细血管密度增加。此外，TUS治疗可提高体内血管内皮生长因子（VEGF）、缺氧诱导因子-1α（HIF-1α）、内皮型一氧化氮合酶（eNOS）和p-Akt的蛋白水平。TUS促进人脐静脉内皮细胞（HUVECs）形成毛细血管样管、迁移和运动。此外，TUS治疗后VEGF、eNOS和p-Akt的蛋白表达增加。总之，在缺血后肢小鼠模型中，TUS治疗通过多种血管生成途径促进出生后新生血管形成。
