缬沙坦对大鼠颈动脉球囊损伤后血管内膜增生和TLR4表达的影响

Effect of valsartan on neointimal hyperplasia and TLR4 expression in carotid artery of balloon injured rat

目的:观察缬沙坦对大鼠颈动脉球囊损伤后血管内膜增生及Toll样受体4(toll like receptor4,TLR4)表达的影响。方法:以1.5F球囊导管建立大鼠颈动脉球囊损伤模型,SD大鼠随机分为假手术组(n=6)、球囊损伤组(n=12)、缬沙坦组(n=12)。造模后第1天开始给予缬沙坦10mg.kg-1.d-1灌胃,假手术组及球囊损伤组灌胃等量蒸馏水,14d后取损伤血管段,组织形态学观察并测定内膜增生情况,实时定量PCR检测血管TLR4mRNA的表达。结果:术后14d,球囊损伤组和缬沙坦组可见明显内膜增生,内膜面积及内膜和中膜面积比均显著大于假手术组,而缬沙坦组上述指标均低于球囊损伤组(P<0.05);球囊损伤组和缬沙坦组TLR4mRNA的表达较假手术组升高,与球囊损伤组比较,缬沙坦可降低球囊损伤诱导的TLR4高表达。结论:缬沙坦可抑制大鼠颈动脉球囊损伤引起的血管内膜增生,其作用可能是通过下调损伤血管TLR4的过表达而实现。

Objective： To investigate the effects of valsartan on neointimal hyperplasia and toll like receptor 4 （TLR4） expression of balloon injured rat carotid artery. Methods：Rat models of carotid artery injury were established with 1.5F balloon. SD rats were randomly divided into sham group （n=6）, model group （n=12） and valsartan treatment group （10 mg · kg^- 1 · d^- 1 n=12）. All rats were sacrificed 14 days after injury, and the injured carotid arteries were harvested. Neointimal hyperplasia and TLR4 mR NA expression were determined by pathologic examination and quantitative real-time PCR, respectively. Results： On the 14th day after operation, obvious neointimal hyperplasia was observed in the model and valsartan treatment group. Compared with the model group, the neointimal area and intimal to media area ratio were significantly decreased in the valsartan treatment group （P〈0.05）. TLR4 mRNA expression was up--regulated in the model and valsartan treatment group. However, there was a significant decrease of TLR4 mRNA in the valsartan treatment group when compared to the model group. Conclusion： Valsartan may inhibit neointimal hyperplasia of rat carotid artery after balloon injury, which may relate to downregulation of TLR4 expression.