摘要/Abstract
摘要： 目的·探讨阿苯达唑（albendazole，ABZ）对小鼠股动脉血管再狭窄的干预作用及可能的机制。方法·采用0.5和1 μmol/L ABZ处理体外培养血管平滑肌细胞（vascular smooth muscle cells，VSMCs）后，分别通过MTT法、Transwell分析及Annexin V-PI染色流式分析评价其对细胞增殖、迁移及凋亡的影响；同时通过蛋白质印迹法进行丝切蛋白（cofilin，CFL）和肌球蛋白轻链（myosin light chain，MLC）的磷酸化机制分析。取10周龄野生型雄性C57BL/6小鼠行股动脉外周套管手术及高脂饲料喂养，建立血管狭窄模型。建模成功后将其随机分为对照组（等体积溶剂）和ABZ组（1.5 mg/d）进行灌胃干预，4周后收集股动脉行苏木精 - 伊红染色分析内膜面积、中膜面积及内膜/中膜（I/M）比值，评价血管再狭窄严重程度。结果·0.5和1 μmol/L ABZ均能够显著抑制VSMCs的增殖和迁移（均P<0.05），而0.5 μmol/L对VSMCs的凋亡无明显影响。ABZ灌胃在小鼠再狭窄模型中能够显著减小新生内膜面积及降低I/M比值，但是对中膜面积并无显著效应。0.5和1 μmol/L ABZ处理均显著抑制CFL去磷酸化和MLC的磷酸化，且呈现浓度依赖的趋势（均P<0.05）。结论·ABZ通过影响细胞骨架蛋白上CFL和MLC的磷酸化，抑制VSMCs迁移和内膜增生，从而对小鼠动脉血管再狭窄发挥治疗效应。
关键词: 阿苯达唑, 血管平滑肌细胞, 内膜增生, 血管阻塞, 机制
Abstract:
Objective · To investigate the effect of albendazole (ABZ) on mouse femoral arteries restenosis and explore its possible mechanism. Methods · Vascular smooth muscle cells (VSMCs) were cultured in vitro with 0.5 and 1 μmol/L ABZ, and evaluated for cell proliferation, migration, and apoptosis by MTT, Transwell assay, and Annexin V-PI staining flow cytometry, respectively; and Western blotting was also used for the analysis of phosphorylation mechanism of cytoskeleton proteins cofilin (CFL) and myosin light chain (MLC). Stenosis was established in the unilateral femoral artery of 10-week-old wildtype male C57BL/6 mice by perivascular cuff placement and high fat chow breeding for 4 weeks. After successful modeling, mice were randomly divided into control group (equal volume of solvent) and ABZ group (1.5 mg/d) for gavage, and femoral arteries were collected 4 weeks later for H-E histological analysis of intimal area, medial area, and intima/media (I/M) ratio to clarify the severity of restenosis. Results · Both 0.5 and 1 μmol/L ABZ could significantly inhibit the proliferation and migration of VSMCs (both P<0.05), while 0.5 μmol/L had no significant effect on the apoptosis of VSMCs. ABZ gavage could significantly reduce the neointimal area and I/M ratio in the restenosis mice, while there were no effects on the median area. Both 0.5 and 1 μmol/L ABZ treatment could significantly inhibit CFL dephosphorylation and MLC phosphorylation, which showed a concentration-dependent trend (both P<0.05). Conclusion · ABZ inhibits VSMCs migration and intimal hyperplasia, via affecting the phosphorylation of cytoskeleton protein CFL and MLC, thereby resulting in therapeutic effects on restenosis of mice.
Key words: albendazole, vascular smooth muscle cell, intimal hyperplasia, vascular occlusion, mechanism
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