奥美沙坦对大鼠移植静脉内膜重构过程中整合素β-3/FAK信号蛋白表达的影响

Expression of integrin β-3/focal adhesion kinase on intimal remodeling of rat vein graft: modulation by olmesartan

目的:观察奥美沙坦对大鼠移植静脉内膜重构过程中整合素β-3(integrinβ-3)黏着斑激酶(focal adhesion kinase,FAK)表达的影响。方法:建立大鼠移植静脉桥模型,将36只雄性SD大鼠被随机分成模型对照组、奥美沙坦组及生理盐水对照组,每组12只。取移植静脉切片、HE染色观察各组血管壁内膜的厚度。采用免疫组化染色法观察各组血管平滑肌细胞(SMC)增殖核抗原(PCNA)的表达。采用Western blot法检测整合素β-3和FAK的表达。结果:与模型对照组相比,奥美沙坦组内膜的厚度明显减轻(P<0.05);PCNA和FAK的表达明显降低(P<0.05)。生理盐水对照组与模型对照组相比,内膜的厚度无明显减轻;PCNA和FAK的表达无明显改变。结论:大鼠移植静脉内膜重构过程中,伴随整合素β-3/FAK信号蛋白的表达,奥美沙坦可抑制大鼠移植静脉内膜重构,此作用可能与下调FAK信号蛋白的表达有关。

AIM： To observe the expression of focal adhesion kinase in rat＇s autologous vein graft and its modulating effect by olmesartan （a specific type Ⅰ angiotensin Ⅱ receptor antagonist）. METHODS： Autologous external jugular veins were grafted to common carotid arteries in 36 male Wistar rats. After surgery, rats were randomly assigned to three groups （12 rats in each） ： model control group, olmesartan group and physiological saline group. The intimal thickness in vein grafts was quantitated in H/E-stained segments. Integrin β-3 and focal adhesion kinase expression levels were assessed by Western blotting, and proliferating cell nuclear antigen （PCNA） was measured by immunohistochemistry. RESULTS： Neointimal hyperplasia was observed in model control group characterized by significant intimal thickening. The expressions of integrin β-3, FAK and PCNA were positive in model control group. Compared with that in model control group, the intimal thickness was significantly attenuated in olmesartan group （P 〈 0. 05 ） and the expressions of FAK and PCNA significantly reduced （P 〈 0. 05 ）. CONCLUSION ： FAK is involved in the restenosis of vein graft in rats. Olmesartan attenuates the restenosis of rat vein graft, possibly through its downregulating effect on FAK.