反义凝血酶受体基因表达抑制大鼠动脉内膜损伤后内膜增生

Expression of antisense thrombin receptor gene inhibits intimal hyperplasia of rat carotid artery after balloon injury

目的 了解凝血酶及其受体在血管损伤后动脉内膜增生中的作用 ,以进一步阐明经皮冠状动脉血管腔内成形术 (PTCA)后再狭窄的发生机制 ,为寻找再狭窄的防治途径提供线索。方法 采用球囊导管损伤动脉内膜的方法建立大鼠颈动脉球囊损伤模型。用纳米粒子包装凝血酶受体重组反义基因质粒pLXSN/ATR ,用保留灌注的方法局部定位转染损伤后的大鼠颈动脉。结果 PCR检测发现重组基因整合 ,RNA斑点杂交观察到实验组大鼠颈动脉壁内有重组反义凝血酶受体基因表达 ,正义凝血酶受体基因的表达受到明显抑制 ,反义基因转染组新生内膜、中膜比例降低了 4 0 9%。结论 反义凝血酶受体重组基因转基因表达对大鼠颈动脉球囊损伤后动脉内膜的增生具有抑制作用 ,提示凝血酶及其受体在PTCA后再狭窄过程中有重要作用 。

Objective To study the mechanism of restenosis after angioplasty and to clarify the effect of thrombin and its receptor on restenosis development Methods Balloon catheter induced injury was adopted to induce intimal hyperplasia of the carotid arteries in rats Antisense thrombin receptor (ATR) cDNA was transfected by perfusing recombinant LXSN ATR plasmid/nanoparticle complex into the segment of the injured carotid artery Results PCR result showed integration of the recombined gene Dot blot showed the expression of antisense TR mediated by recombinant LXSN ATR plasmid/nanoparticle complex in the wall of common carotid arteries of the experimental group rats, which enabled to inhibit TR gene expression and intimal hyperplasia of the injured arteries Conclusions Thrombin and its receptor play an important role in the formation of neointima after the injury, which provides a potential clue in developing a new approach for prevention and treatment of restenosis after angioplasty