波生坦对大鼠颈动脉再狭窄的影响及其病理机制

Effect and pathogenetic study of Bosentan on carotid artery restenosis in rat

目的探讨波生坦对大鼠颈动脉再狭窄的影响及其病理机制。方法选取Wistar大鼠65只,随机分为假手术组、损伤组及波生坦组。损伤组及波生坦组模拟临床经皮冠状动脉形成术(PTCA)过程行左颈总动脉球囊损伤致内膜剥落,波生坦组给予波生坦100mg·kg-1.d-1灌胃(术前1d直至处死)。观测术后不同时相点的内膜,中膜动态增殖情况,并采用免疫组化法检测α-平滑肌肌动蛋白(α-SMA)和抗增殖细胞核抗原(PCNA)。结果损伤组术后28d新生内膜增生达峰值,波生坦组术后14d内膜增生达峰值。术后14、28、45d波生坦组内膜面积较损伤组明显减小(P<0.001)。术后14d的波生坦组内膜PCNA的阳性率与损伤组比较显著降低(P<0.01)。术后14dα-actin的阳性表达率较损伤组明显增加(P<0.01)。结论波生坦组可通过抑制血管内膜过度增殖及减少血管平滑肌细胞的增殖,转型和迁移而有效预防PTCA术后再狭窄的发生。

Objective To investigate the effect and pathogenetic study of Bosentan on carotid artery restenosis in rat. Methods 65 Wistar rats were divided randomly into 3 groups： sham, injury and Bosentan groups. The balloon catheter injury was performed on left common carotid artery of rat by imitating the process of percutaneous transeoronary angioplasty （PTCA） in injury and Bosentan groups. 100 mg · kg- 1· d-1 Bosentan was administrated intragastricly to rats of Bosentan group （from 1 day to being killed）. The process of neointimal and media hyperplasia was observed and α-aetin and proliferation cell nuclear antigen （PCNA） expressions were determined. Results Arterial neointima hyperplasia reached summit at 28 days in injury group and at 14 days in Bosentan group. Neointimal and media area of Bostentan at different time （14th ,28th ,45th day） were significantly decreased compared with injury group （P 〈 0. 001 ）. The positive rate of PCNA increased statistically in Bosentan group than that of injury group at 14th day （P 〈 0.01 ）. The positive rat of α-actin cell increased significantly in Bosentan group compared with injured group （ P 〈0.01 ） at 14th day. Conclusions Bosentan can effectively prevent artery rest- enosis by inhibiting neointimal hyperplasia and reducing the proliferation, migration, transconformation of vascular smooth muscle cells.