大鼠移植静脉再狭窄过程中黏着斑激酶的活化及奥美沙坦的干预作用

The Phosphorylation of Focal Adhesion kinase in The Restenosis of Rat's Vein Graft:Modulation by Olmesartan

目的研究黏着斑激酶(FAK)在大鼠移植静脉再狭窄过程中的作用,并研究奥美沙坦的干预效应。方法建立大鼠颈外静脉移植模型,将40只雄性大鼠随机分成:1)假手术组;2)模型组;3)奥美沙坦组;4)生理盐水组等4组。观察各组血管壁内膜厚度及内膜/中膜(I/M);采用免疫组化方法观察各组血管平滑肌细胞增殖核抗原(PCNA)及平滑肌肌动蛋白(α-SM actin)表达;采用 western-blot 方法检测 FAK 及磷酸化 FAK 的表达。结果模型组与假手术组相比,内膜明显增厚(P<0.01),I/M 明显增加(P<0.01),PCNA 表达明显增加(P<0.01),α-SMactin、FAK、磷酸化 FAK 叫显增加(P<0.05);奥美沙坦组与模型组相比,内膜厚度、I/M 明显减轻(P<0.05),PC-NA、α-SM actin、磷酸化 FAK 表达明显降低(P<0.05)。结论 FAK 活化参与了大鼠移植静脉再狭窄过程,奥美沙坦可以抑制大鼠移植静脉再狭窄,这种作用可能与减轻局部 FAK 活化有关。

Objective To study the expression and phosphorylation of focal adhesion kinase（FAK） in rat＇s autologous vein graft and the olmesartan modulating effect. Methods Autologous external jugular veins were grafted to common carotid arteries in 40 male Sprague Dawley rats. After surgery, rats were randomly assigned to the fol- lowing groups： sham;control;olmesartan treatment（ 10mg/kg. d by gavage）; or physiological saline. The intimal thickness, the I/M in vein grafts was quantitated by HE stain. The expression and phosphorylation of focal adhesion kinase were assessed by Western-blotting, PCNA and α-smooth muscle actin were measured by immunohistochemistry. Results Neointimal hyperplasia in control group was characterized by significantly increased intimal thickeness I/M（P〈0.01 ）. The expression of FAK, phosphorylated FAK, PCNA and α-smooth muscle actin in model control group were significantly higher than in the sham group （P〈0. 05 ）; Compared to the control group, olmesartan significantly attenuated intimal thickness and I/M（ P〈0. 05）, and the reduced the expression of phosphorylated FAK, α-smooth muscle actin and PCNA（P〈0. 05）. Conclusion The phosphorylation of FAK was associated with the restenosis of rat＇s vein graft; Olmesartan attenuate the restenosis and downregulated FAK local expression.