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低频超声联合微泡促进多发性大动脉炎血管平滑肌细胞凋亡的生物学效应

Biological effects of low-frequency ultrasound combined with microbubbles on promoting apoptosis of vascular smooth muscle cells in Takayasu arteritis

  • 摘要: 目的:探讨超声联合微泡技术影响多发性大动脉炎(Takayasu arteritis, TA)血管平滑肌细胞的变化,为该类疾病的预防和治疗提供依据。方法:通过手术获取TA增生进展期、炎症硬化期及经皮血管腔内成形术(percutaneous transluminal angioplasty, PTA)后再狭窄期血管平滑肌细胞进行体外培养,建立偶联抗体的靶向超声微泡剂,采用20 kHz低频超声辐照150 s后培育24 h进行研究观察。结果:通过超声微泡处理后3组细胞存活率有明显差异(P<0.01);相较其他两组,PTA后再狭窄期血管平滑肌细胞反应更敏感(P<0.05),其培养基活性氧(ROS)明显上升(P<0.01),而超氧化物歧化酶(SOD)活性明显降低(P<0.01),细胞凋亡水平明显增加(P<0.01)。结论:超声微泡联合处理可能对PTA后再狭窄期的治疗更有效果,超声微泡对TA血管平滑肌细胞具有明显的抑制与促凋亡的生物学效应。

     

    Abstract: Objective:To explore the effects of ultrasound combined with microbubble technology on the changes of vascular smooth muscle cells (VEMCs) in Takayasu arteritis (TA), and provide evidence for the prevention and treatment. Methods:Primary VEMCs in three different phases, including the TA proliferative progression phase, inflammatory sclerosis phase, and post-percutaneous transluminal angioplasty (PTA) restenosis phase, were obtained during surgery. Microbubbles with targeted functions were specifically bind to cells via the coupling-specific antibodies. The optimum ultrasound conditions, which consisted of ultrasound irradiation for 150 s and 24 h incubation, were determined and used in the subsequent experiments. Results:Significant differences were observed for the cell viability among cells of the three different phases (P<0.01). The cells in the post-PTA restenosis phase were more sensitive to the treatment than those in other two phases (P<0.05), the reactive oxygen species (ROS) activity in the cell culture medium from the ultrasound-microbubble combined group was significantly increased (P<0.01), while the superoxide dismutase (SOD) activity was significantly decreased (P<0.01). Apoptosis levels were significantly increased in the ultrasound-microbubble group (P<0.01). Conclusions:Ultrasound-microbubble combination therapy is more effective for the treatment of post-PTA restenosis, and targeted microbubbles could significantly enhance the VEMCs apoptosis.

     

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