目的 观察辛伐他汀对大鼠损伤后狭窄颈总动脉中碱性成纤维细胞生长因子(bFGF) mRNA和细胞外信号调节激酶1/2 (ERK1/2) mRNA表达的影响.方法 健康雄性SD大鼠80只,随机分为假手术组、模型组、辛伐他汀低剂量和高剂量组,制备颈总动脉狭窄模型,辛伐他汀低剂量组和高剂量组于术前3d起分别给予辛伐他汀5、10 mg·kg-1·d-1进行灌胃,连续给药17d后处死,苏木精-伊红染色观察左颈总动脉形态学变化；反转录聚合酶链式反应法测定血管壁组织的bFGF mRNA与ERK1/2 mRNA表达.结果 与假手术组比较,模型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；辛伐他汀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；辛伐他汀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.与假手术组比较,其他各组颈总动脉bFGF mRNA、ERK1/2 mRNA的表达均有显著增高,差异有统计学意义(P＜0.01)；与模型组比较,辛伐他汀低剂量组bFGF mRNA、ERK1/2 mRNA的表达差异无统计学意义(P＞0.05),辛伐他汀高剂量组则明显降低,差异有统计学意义(P＜0.01)；辛伐他汀高剂量组颈总动脉bFGF mRNA和ERK1/2 mRNA表达与低剂量组比较明显降低,差异有统计学意义(P＜0.05).结论 辛伐他汀可通过抑制bFGF mRNA和ERK1/2 mRNA的表达抑制VSMC增殖,实现其抗血管损伤后狭窄的作用.%Objective To investigate the expressions of basic fibroblast growth factor (bFGF) mRNA and extracellular signal-regulated kinase l/2( ERK1/2) mRNA in injuried carotid artery with stenosis in rats and the effect of simvastatin on their expressions. Methods Eighty healthy male SD rats were randomly divided into sham group,model group,low doses simvastatin group and high doses simvastatin group. Animal model of vascular restenosis was established, the rats of low and high doses simvastatin groups were respectively lavaged with 5 mg · kg-1· d-1 and 10 mg · kg-1· d-1 simvastatin three days before the operation. All animals were sacrificed after giving simvastatin for 17 days. The morphologic changes of left common carotid artery were observed by haemaloxylin-eosin staining; the mRNA expressions of bFGF and ERKl/2 in carotid artery of each group were detected by reverse transcription polymerase chain reaction. Results Compared with sham group,the vascular smooth muscle cell (VSMC) in the tunica media was obviously proliferated and disordered arrangement, the lumen of the carotid artery became more stenosis in model group; the tunica inlinia 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 strait-ness became more weaken in the low doses group;the tunica intima vasorum of the carotid artery was smooth,and the prolifera- tion of VSMC in the tunica media vasorum was obviously decreased, while its straitness was more light in the high doses group. Compared with the sham group,the expressions of bFGF mRNA and ERK1/2 mRNA in carotid artery were more significantly higher in other groups(P<0.01) {compared with model group,there was no statistically significant in the expression of bFGF mRNA and ERK1/2 mRNA in low doses simvastatin group(P>0.05) ,but in high doses simvastatin group they decreased ob-vicusly (P<0.01). Compared with low doses simvastatin group,the expressions of bFGF mRNA and ERK1/2 mRNA in high doses simvaslatin group decreased obviously,the differences were significant (P<0.05). Conclusion Simvastatin might inhibit the expression of bFGF mRNA and ERK1/2 mRNA to suppress VSMC proliferation and inhibit carotid arteries stenosis.
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