苯妥英钠对大鼠颈总动脉球囊损伤后内膜增生的影响

Effects of Phenytoin on Neointima Formation After Balloon Injury in Rat Carotid Artery

目的研究苯妥英钠促进创伤修复的特殊药理学作用在大鼠颈总动脉球囊损伤后内膜修复过程中的影响。方法采用大鼠颈总动脉内膜球囊损伤模型,术后大鼠分为苯妥英钠组和损伤组。术后28天处死大鼠,取双侧颈总动脉,石蜡包埋、切片后进行血管病理学染色分析。结果术后28天,苯妥英钠组内膜面积(0.154±0.018mm2比0.204±0.054mm2,P<0.01)、内膜/中膜面积比(1.70±0.08比2.26±0.46,P<0.01)、再狭窄率(59.5%±3.2%比75.9%±13.3%,P<0.01)均小于损伤组,管腔面积(0.106±0.024mm2比0.063±0.034mm2,P<0.01)大于损伤组;内膜细胞密度(72.18±20.08/cm2比84.85±10.77/cm2,P<0.05)、增殖细胞核抗原阳性细胞数(9.89±7.63个/200倍视野比23.03±13.95个/200倍视野,P<0.01)和α-平滑肌肌动蛋白阳性细胞数(30.91±20.05/200倍视野比61.81±16.57个/200倍视野,P<0.01)均小于损伤组;新生内膜中有少量胶原组织增生,但组间血管胶原面积和密度均无统计学差异(P>0.05)。结论大鼠颈总动脉球囊损伤后28天,苯妥英钠可以抑制损伤血管内膜增生过程中的细胞增生,促进细胞外基质合成,对血管损伤后内膜增生和管腔狭窄具有抑制作用。

Aim To investigate the special pharmacological effect of phenytoin on the healing process after ballon injury in rat carotid artery. Methods Study was performed on rat model of balloon-injury in common carotid artery. Rats survived from successful operation were divided into phenytoin group and injury group. On the 28th day after operation, rats were anesthetized, then the left carotids and the corresponding part of the right carotids were separated, embedded with paraffin, sectioned into 5μm and stained. Results On the 28th day after operation, the intima area （0. 154 ± 0. 018 mm^2 vs 0.204 ± 0.054 mm^2, P〈0.01）, intima/media area （1.70±0.08 vs 2.26±0.46, P〈0.01） and the rate of restenesis （59.5%±3.2% vs 75.9% ± 13.3 %, P 〈 0.01 ） in phenytoin group were all less than dlose in injury group, while lumen area （0. 106 ± 0.024 mm^2 vs 0.063 ± 0.034 mm^2, P 〈 0.01 ） was larger than that in injury group, cell density in intima （ 72.18 ± 20.08/cm^2 vs 84.85 ± 10.77/cm^2 , P 〈 0.05）, proliferating cell nuclear antigen （PCNA） positive cell cotmting （9.89 ± 7.63 per 200 magnification vs 23.03 ± 13.95 per 200 magnification, P 〈 0.01 ） and α-smooth muscle actin positive cell counting （30.91 ± 20.05 per 200 magnification vs 61.81 ± 16.57 per 200 magnification, P 〈 0.01 ） were all smaller than those in injury group; trader polarized light, collagen could be visualized deposite in intima, but there were no statistic difference in collagen area and density （ P 〉 0.05）. Conclusion 28 days after vascular injury, phenytoin can decrease the cell number in neointima and promote the synthesis of extracellular matrix which result in diminished neointima thickening.