曲匹地尔抑制大鼠胸主动脉球囊损伤后肌内膜增殖

Inhibitory Effect of Trapidil on the Myointimal Hyperplasia Following Rat's Thoracic Aorta Injury by Balloon Catheter

以 2 F球囊导管剥脱大鼠胸主动脉内膜后 ,采用光镜和电镜定性观察和计算机图像分析定量方法研究曲匹地尔对大鼠胸主动脉内膜损伤后肌内膜增殖的影响。结果表明 ,与假手术组比较 ,单纯血管损伤组的动脉壁增厚和肌内膜增生明显 ,内皮下内弹力板破坏 ,血管平滑肌细胞多呈合成表型并大量迁移到血管内膜。曲匹地尔处理后 ,动脉壁明显变薄 ,肌内膜增生明显减弱 ,血管平滑肌细胞多呈收缩表型 ,较少平滑肌细胞迁移至内膜下。计算机图像定量分析表明血管损伤后 14d,内膜与中膜面积比和厚度比分别增加 34 5 %和 36 4% (均为 P<0 .0 1) ,曲匹地尔 10 m g/ (kg· d)、 2 0m g/ (kg· d)和 40 m g/ (kg· d)给药 17d,内膜与中膜的面积比分别降低 48%、 6 3%和 6 5 % (P值分别小于 0 .0 5、0 .0 1和 0 .0 1) ,使内膜与中膜的厚度比分别降低 5 0 %、 6 3%和 72 % (均为 P<0 .0 1) ,且抑制程度与曲匹地尔剂量有明显相关性 (r值分别为 - 0 .72 9和 - 0 .75 7,均为 P<0 .0 1)。提示 :曲匹地尔能明显抑制大鼠血管损伤后肌内膜的形成和血管管壁增厚。

After the thoracic aorta intima of rats was denuded by 2 Forgarty catheter, the morphology of arterial intima and media was studied by optical microscopy, electron microscopy and image analysis system. The results showed that the thickened wall of artery and myointimal hyperplasia in artery injured group were more obvious than in the sham group. The internal elastic lamina was partly damaged, and the smooth muscle cells in media changed from contractile phenotype into synthetic phenotype and many of them migrated in the intima after artery injured. After treated with trapidil, the thickness of arterial walls became thin and myointimal hyperplasia was obviously lessened. The smooth muscle cells presented synthetic phenotype and fewer of them migrated in the intima. The results of image analysis showed the ratio of intimal to medial areas and intimal to medial thickness in the group I were increased by 345 % and 364 % as compared with those in the sham group 14 days after arterial injury, respectively (both P<0.01). After administration of trapidil 10 mg/(kg·d), 20 mg/(kg·d) and 40 mg/(kg·d) for 17 days, the ratio of intimal to medial areas were decreased by 48 %, 63 % and 65 % respectively (P<0.05, 0.01 and 0.01 respectively), and intimal to medial thickness were decreased by 50 %, 63 %, and 72 %, respectively (all P<0.01), in a dose-dependent manner. It is suggested that the vascular neointima formation, stenosis within the artery and intimal thickening following arterial injury were significantly inhibited by trapidil.