曲尼司特抑制大鼠胸主动脉球囊损伤后再狭窄

Tranilast in preventing restenosis after rat thoracic aorta balloon injury

目的探讨曲尼司特对大鼠球囊损伤血管新生内膜增殖反应的干预作用及对细胞周期调控因子表达的影响。方法术后14 d处死动物,HE染色法观察形态学变化;用免疫组化方法鉴定各组p27的表达;另外用流式细胞术测定平滑肌细胞各期(G1期,S期,G2/M期)百分比。结果①假手术组无新生内膜形成,模型组内膜增生显著,曲尼司特组内膜增生减轻[(0.32±0.05)mm2vs(0.14±0.01)mm2,P<0.01]。②免疫组织化学染色显示,模型组新生内膜处p27低表达,曲尼司特组新生内膜p27表达强烈(20.8±1.7vs10.5±0.7,P<0.01)。③流式细胞术显示,与模型组相比,曲尼司特组平滑肌细胞处于增殖期的细胞比例明显降低[(27.5±1.1)%vs(13.5±1.5)%,P<0.01]。结论曲尼司特能抑制血管平滑肌细胞增殖,其抗增殖机制可能与细胞周期调控和上调p27相关。

AIM To investigate the influence of tranilast on cell cycle modulatory factors and proliferation response of vascular smooth muscle cell after balloon angioplasty. METHODS Aortic tissues were harvested at day 14 after injury and HE staining and immunohistochemistry staining were used to measure the protein expressions of cell cycle modulatory factors p27. Flow Cytometry （FCM） was applied to determine the cell cycle of the neointima. RESULTS ① Neointima formation was apparent in the arteries from the operation group and was reduced much more in the tranilast group [ （0.32 ±0.05 ）mm^2 vs （0.14 ± 0.01 ） mm^2, P 〈0.01 ） ]. ②Immunohistochemistry staining revealed that p27 protein expressions were low in the neointima of the model group and were significantly increased by tranilast （20.8 ± 1.7 vs 10.5 ± 0.7, P 〈0.01 ）. ③ FCM showed that in the model group, the percentage of S phase of smooth muscle cells was high but declined in the tranilast group [ （27.5 ± 1. 1 ）% vs （ 13.5 ± 1.5 ）%, P 〈 0.01 ]. CONCLUSION Tranilast surpresses neointima formation after artery injury by up - regulation of p27.