辛伐他汀对大鼠颈总动脉损伤后再狭窄时碱性成纤维细胞生长因子与磷酸化细胞外信号调节激酶蛋白表达的影响

Effect of simvastatin on the expression of bFGF and p-ERK1/2 in vessel in rats with carotid artery injury with restenosis

目的:探讨辛伐他汀对大鼠颈总动脉损伤后再狭窄时碱性成纤维细胞生长因子(bFGF)与磷酸化细胞外信号调节激酶(p-ERK1/2)蛋白表达的影响。方法:建立血管损伤后再狭窄动物模型,分为假手术组、手术组、低剂量组和高剂量组,低、高剂量组术前3d分别用5mg/(kg·d)和10mg/(kg·d)辛伐他汀灌胃,术后14d处死所有实验动物,各取2～4cm左侧颈总动脉用于实验。HE染色观察左颈总动脉形态学的变化;Westernblot检测血管bFGF、p-ERK1/2蛋白的表达。结果:与假手术组比较,手术组血管中膜血管平滑肌细胞(VSMC)增殖显著,排列紊乱,向管腔及内弹力板方向增生扩展,管腔严重狭窄;低剂量组血管内膜相对光滑,中膜VSMC排列趋于规整,管腔狭窄程度较轻;高剂量组血管内膜比较光滑,中膜VSMC增殖程度显著降低,VSMC排列规整,管腔狭窄程度明显减轻。与对照组比较,其他各组颈总动脉bFGF、p-ERK1/2的表达差异均有显著性(P<0.01);与手术组比较,低剂量组bFGF、p-ERK1/2的表达差异无显著性;高剂量组则差异有显著性(P<0.01),高剂量组与低剂量组比较差异亦有显著性(P<0.05)。结论:辛伐他汀可能通过抑制bFGF和p-ERK1/2蛋白的表达达到抑制VSMC增殖,减轻血管再狭窄的作用。

Objective To explore the effect of simvastatin on the expression of bFGF and lp-ERK1/2 in restenosal vessel after carotid artery injury in rats. Methods Animal model of vascular restenosis was established, the rats were randomly divided into four groups： sham group, operation group, low-dose simvastatin group and high-dose simvastatin group, the rats of low- and high- dose groups were respectively intragastrical with 5 mg/（kg. d） and 10 mg/（kg. d） simvastatin. All used animals were sacrificed 14 days after surgery. The changes of tunica media vasornm were observed by HE staining; the expression of bFGF and p-ERK1/2 was detected by Western blot. Results Compared with the sham group, the VSMC in the tunica media was obviously proliferated and disordered arrangement, the lumen of the carotid artery became more stenosal in the operation group ; The tunica intima of the carotid artery was more relatively smooth, the proliferation of VSMC in the tunica media was more regularly arrangement, while the lumen of the carotid artery＇s degree of straitness decreased in the low-dose group; The tunica intima vasornm of the carotid artery was smooth, and the proliferation of VSMC in the tunica media vasorum was obviously decreased, while its straitness was more light in the high-dose group. Compared with the sham group, the expression of bFGF and p-ERK1/2 increased significantly in other groups （P 〈 0.01 ） ; Compared with the operation group, the change of bFGF and p-ERK1/2 was uneonspieuous in low-dose group and was obvious in high doses group （P 〈 0.01 ） ; There was significant difference between low-dose group and high-dose simvastatin group （P 〈 0.05）. Conclusions Simvastatin might suppress VSMC proliferation and reduce the role of vascular restenosis through inhibiting the expression of bFGF and p-ERK1/2.