Sun Shougang, Zhang Quan, Wang Qiongying, Wu Qiang, Xu Guangli, Chang Peng, Hu Hao, Bai Feng
Department of Cardiology, Lanzhou University Second Hospital, Lanzhou, Gansu, 730030, China.
Department of Cardiology, Pingliang People's Hospital, Pingliang, 744000, China.
Pathol Res Pract. 2018 Sep;214(9):1303-1308. doi: 10.1016/j.prp.2018.02.019. Epub 2018 Feb 21.
To observe the effect of local administration of thalidomide on neointimal formation after balloon-induced carotid artery injury in rats.
Forty-eight male Sprague-Dawley rats were randomly divided into 3 groups (n = 16): Sham operation group (group A), alone operation group (group B) and Thalidomide group (group C). The carotid arteries of group B and group C were injured by a conventional percutaneous transluminal coronary angioplasty (PTCA) balloon catheter. Group C was treated by local delivery of thalidomide, and group B did not receive thalidomide. The arteries of group A were not injured. Seven and 14 days after balloon injury, rats were sacrificed. Serum concentrations of vascular endothelial growth factor (VEGF) and tumor necrosis factor-α (TNF-α) were measured using enzyme-linked immunosorbent assay (ELISA). Neointima area, lumen area, macrophage infiltration and local expression of VEGF were measured using morphometric and immunohistochemical analyses. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) was used to examine VEGF mRNA expression.
The VEGF levels were significantly increased in group B than in group C at 7 days (4.82 ± 0.17 pg/mL vs 0.98 ± 0.1 pg/mL, P < 0.01) and 14 days (6.3 ± 0.16 pg/mL vs 1.03 ± 0.09 pg/mL, P < 0.01). The TNF-α levels were also significantly increased in group B than in group C at 7 days (83 ± 1.01 pg/mL vs 76.37 ± 0.75 pg/mL, P < 0.01) and 14 days (84.06 ± 1.11 pg/mL vs 78.46 ± 0.94 pg/mL, P < 0.01). However, the area of neointimal formation was significantly reduced in group C than in group B at 14 days (0.07± 0.01 mm vs 0.12± 0.04 mm, P < 0.01). Macrophage infiltration and local expression of VEGF in the injured arteries were significantly reduced in group C than in group B at 14 days. VEGF mRNA expression was significantly reduced in Group C than in group B at 14 days (6.3 ± 0.16 vs 1.02 ± 0.1, P < 0.01).
Thalidomide, which is a specific VEGF inhibitor, significantly inhibited neointimal hyperplasia and vascular restenosis after balloon injury to the carotid artery in rats, thus potentially providing a novel method for the prevention and treatment of restenosis, especially in-stent restenosis.
观察沙利度胺局部给药对大鼠球囊损伤颈动脉后新生内膜形成的影响。
48只雄性Sprague-Dawley大鼠随机分为3组（n = 16）：假手术组（A组）、单纯手术组（B组）和沙利度胺组（C组）。B组和C组大鼠的颈动脉采用传统经皮腔内冠状动脉成形术（PTCA）球囊导管进行损伤。C组采用沙利度胺局部给药治疗，B组未接受沙利度胺治疗。A组大鼠的动脉未损伤。球囊损伤后7天和14天，处死大鼠。采用酶联免疫吸附测定（ELISA）法检测血清血管内皮生长因子（VEGF）和肿瘤坏死因子-α（TNF-α）浓度。采用形态学和免疫组织化学分析方法测量新生内膜面积、管腔面积、巨噬细胞浸润及VEGF的局部表达。采用实时逆转录聚合酶链反应（RT-PCR）检测VEGF mRNA表达。
7天时，B组VEGF水平显著高于C组（4.82±0.17 pg/mL vs 0.98±0.1 pg/mL，P < 0.01）；14天时，B组VEGF水平也显著高于C组（6.3±0.16 pg/mL vs 1.03±０.09 pg/mL，P < 0.01）。7天时，B组TNF-α水平也显著高于C组（83±1.01 pg/mL vs 76.37±0.75 pg/mL，P < 0.０1）；14天时，B组TNF-α水平同样显著高于C组（84.06±1.11 pg/mL vs 78.46±0.94 pg/mL，P < 0.01）。然而，14天时，C组新生内膜形成面积显著小于B组（0.07±0.01 mm vs 0.12±0.04 mm，P < 0.01）。14天时，C组损伤动脉中的巨噬细胞浸润及VEGF的局部表达显著低于B组。14天时，C组VEGF mRNA表达显著低于B组（6.3±0.16 vs 1.02±0.1，P < 0.01）。
沙利度胺作为一种特异性VEGF抑制剂，可显著抑制大鼠球囊损伤颈动脉后的新生内膜增生和血管再狭窄，从而可能为再狭窄尤其是支架内再狭窄的防治提供一种新方法。
