颈总动脉损伤大鼠成纤维细胞生长因子受体1、p21ras表达与辛伐他汀的抑制效应

背景：辛伐他汀可通过抑制血管平滑肌细胞增殖发挥抗血管狭窄作用,但其作用机制尚不完全清楚。目的：观察辛伐他汀对血管损伤后狭窄时成纤维细胞生长因子受体1、p21ras蛋白表达的影响。方法：建立SD大鼠颈总动脉损伤模型,随机分为假手术组、模型组、低剂量和高剂量辛伐他汀组,后2组分别于术前3d灌胃辛伐他汀5,10mg/（kg？d）直至术后14d。结果与结论：大鼠颈总动脉损伤后：①苏木精-伊红染色显示,血管中膜血管平滑肌增殖显著,排列紊乱,管腔严重狭窄;应用辛伐他汀后血管内膜相对光滑,中膜血管平滑肌细胞排列趋于规整,管腔狭窄程度有不同程度减轻。②Western blot检测显示,颈总动脉成纤维细胞生长因子受体1、p21ras表达明显升高（P〈0.05）,低剂量辛伐他汀干预后两种蛋白表达无明显变化,应用高剂量辛伐他汀干预后两种蛋白表达明显下降（P〈0.05）。表明辛伐他汀可能通过抑制成纤维细胞生长因子受体1、p21ras蛋白的表达抑制血管平滑肌细胞增殖,减轻血管损伤后狭窄。

Inhibitory effect of simvastatin on the expression of fibroblast growth factor receptor 1 and p2lras following common carotid artery injury in rats

BACKGROUND：Simvastatin can inhibit the proliferation of vascular smooth muscle cells and play a role in anti-vascular stenosis,but its mechanism is not fully understood.OBJECTIVE：To explore the effect of simvastatin on the expression of fibroblast growth factor 1 and p21ras in stenotic vessels after common carotid artery injury in rats.METHODS：Animal model of common carotid artery injury was established.The rats were randomly divided into four groups：sham-operation group,model group,low-dose simvastatin group and high-dose simvastatin group.The rats in the latter two groups were treated with 5 mg/（kg·d） and 10 mg/（kg·d） simvastatin by gavage respectively,from 3 days before surgery to 14 days after surgery.RESULTS AND CONCLUSION：Hematoxylin-eosin staining showed that the vascular smooth muscle cells in the tunica media was obviously proliferated and disordered arranged,the lumen of the carotid artery became more stenosis.After treated with simvastatin,the tunica intima of the carotid artery was relatively smooth,the vascular smooth muscle cells in the tunica media were more regularly arranged and the straitness degree of the carotid artery lumen weakened.Western blot analysis showed that the expression of fibroblast growth factor 1 and p21ras protein increased significantly（P 0.05）.There was no obvious change in the two protein expressions after low-dose simvastatin treatment.The expression of fibroblast growth factor 1 and p21ras decreased significantly after high-doses simvastatin treatment（P 0.05）.These findings indicate that simvastatin may suppress the expression of vascular smooth muscle cells and reduce vascular stenosis by inhibiting the expression of fibroblast growth factor 1 and p21ras.