替米沙坦对大鼠血管损伤性重塑过程中粘着斑激酶表达和活化的影响

Effect of Timisartan on Focal Adhesion Kinase Expression in Vascular Remodelling After Artery Injury in Rats

目的研究血管紧张素受体拮抗剂替米沙坦对血管损伤性重塑及其过程中粘着斑激酶表达和活化的影响。方法建立大鼠主动脉内皮剥脱术后再狭窄模型,将雄性大鼠随机分为对照组、模型组和替米沙坦组,每组12只。30天后取损伤部位血管段进行形态学观察,逆转录聚合酶链反应法测定粘着斑激酶mRNA的表达,Westernblot法测定粘着斑激酶蛋白总量和磷酸化蛋白含量。结果术后30天,模型组主动脉内膜明显增厚,粘着斑激酶mRNA水平明显增高,蛋白含量及磷酸化水平均明显增加,而替米沙坦组血管内膜增生程度明显减轻,粘着斑激酶mRNA表达活性明显降低,粘着斑激酶蛋白含量及磷酸化水平明显降低。结论替米沙坦可明显减轻大鼠血管内膜剥脱术后血管内膜增生程度,抑制血管损伤后粘着斑激酶表达与活化。替米沙坦的抗血管损伤性重塑作用可能与抑制粘着斑激酶表达与活化有关。

Aim To examine the effect of timisartan on expression and activity in vascular remodeling after artery injury in rats. Methods The rat models of balloon endothelial denudation were builded. Male Wistar rats were randomized to three groups： nomal control group （n=12）, model group （n=12） and timisartan group （n=12）. The rats in timisartan group were supple diet with timisartan 40 mg/（kg·d）. The animals were sacrificed at 30 days after the injury. Western blot were used to detect the expression and activity of focal adhesion kinase （FAK） with RT-PCR or Western blot method. Hyperplasia of intima were observed. Results Compared with the control group, hyperplasia of intima were significantly increased, the expression of FAK mRNA, protein and its activity were significantly increased in model group at 30 days after the injury. Compared with the model group, hyperplasia of intima were significantly lower, the expression of FAK mRNA, the expression of FAK protein and activity were significantly decreased inTimisartan group. Conclusion Timisartan significantly inhibited artery wall remodelling and expression and activity of FAK in the rat model of artery injury. The mechanisms of Timisartan inhibiting artery wall remodelling could involve inhibition of expression and activity of FAK.