阿托伐他汀抑制球囊损伤后腹主动脉碱性成纤维细胞生长因子及蛋白激酶B的表达

Atorvastatin inhibits balloon injury-induced basic fibroblast growth factor and protein kinase B expression in abdominal aorta in rabbits

目的观察阿托伐他汀对球囊损伤后兔腹主动脉碱性成纤维细胞生长因子(bFGF)及蛋白激酶B(PKB)表达的影响。方法将72只大耳白兔随机分为假手术组、模型组和阿托伐他汀2.5 mg·kg-1·d-1灌胃组(均n=24)。对球囊损伤后不同时间段的兔腹主动脉标本行HE染色,观察血管内膜增殖情况;免疫组化检测观察bFGF在增殖内膜中的表达;Western-blot检测观察PKB的表达。结果假手术组动脉未见有血管平滑肌细胞(VSMC)迁移以及内膜增生;模型组7 d时,开始出现新生内膜,主要由2～3层血管平滑肌细胞组成。术后14 d、28 d时可见明显新生内膜产生,主要由迁移的VSMC和细胞外基质组成,VSMC排列紊乱。阿托伐他汀组术后14 d、28 d时也可见内膜增殖,但增殖程度与模型组相比明显降低(P<0.01)。术后7 d、14 d、28 d时模型组bFGF、PKB的表达较术前明显增加,且成上升趋势,假手术组未见明显变化;阿托伐他汀组与模型组比较,术后7 d时未见明显差异,术后14 d、28 d时bFGF和PKB表达显著减少(P<0.05或P<0.01)。结论阿托伐他汀抑制球囊损伤后内膜增生,其可能机制是抑制bFGF和PKB的表达。

AIM To investigate the effects of atorvastatin on expression of basic fibroblast growth factor （bFGF） and protein kinase B （PKB） in abdominal aorta after balloon injury in rabbits. METHODS Seventy- two rabbits were randomly divided into three groups （n = 24）, including sham group, balloon injury model group and atorvastatin treatment （2.5 mg·kg^-1·d^-1, ig） group. Abdominal artery was collected at different time points. Intimal hyperplasia was studied by histological morphology method. The expression of bFGF and PKB in the tissues was examined by immunohistoehemistry staining and Western-blot, respectively. RESULTS Intimal hyperplasia was detectable at day 7 after balloon injury, and became more obvious at days 14 and 28. No change was observed in the sham group. In the atorvastatin treatment group, the level of intimal hyperplasia was inhibited. The expressions of bFGF and PKB were increased significantly at days 7, 14 and 28 after balloon injury in the model group compared with those in the sham group （P 〈 0.01 ）. The expression of bFGF and PKB were decreased significantly in at days 14 and 28 in the atorvaststin group than those in the model group （P 〈 0.05 or P 〈 0.01 ）. CONCLUSION Atorvaststin blocks balloon injury- induced the upregulation of bFGF and PKB, indicating that atorvaststin may play an important role in intimal hyperplasia mediated by regulating the expressions of bFGF and PKB.