西立伐他汀对动脉平滑肌细胞周期调控因子和增殖反应的干预作用

The Influence of Cerivastatin on Proliferation Response of Vessel Smooth Muscle Cell and Cell Cycle Modulatory Factors after Vascular Baloon Injury in Thoracic Aortae of Rats

目的 :探讨西立伐他汀对大鼠动脉球囊损伤后平滑肌细胞周期调控因子 p2 7、CDK2、PCNA表达和增殖反应的干预作用。方法 2 4只大鼠随机分为假手术组、手术组、西立伐他汀组 ,8只 /组。后两组行球囊内皮剥脱术 ,西立伐他汀组于术前 3d开始灌胃法给予西立伐他汀 ,0 .1mg/kg·d-1,假手术组和手术组同期给予等量生理盐水灌胃。术后 14d处死所有动物 ,取胸主动脉进行HE染色及p2 7、CDK2、PCNA免疫组织化学染色 ,并进行血管形态学检测。结果假手术组无新生内膜形成 ,手术组内膜增生显著 ,他汀组内膜增生减轻 (I/M :41.5 0± 9.5 4vs14.6 7± 7.36 ,P <0 .0 1)。免疫组织化学染色显示假手术组 p2 7高表达 ,CDK2、PCNA未见表达 ;手术组新生内膜处 p2 7低表达 ,CDK2、PCNA高表达 ;他汀组新生内膜p2 7表达强烈 ,而CDK2、PCNA表达被抑制。结论在活体内 ,他汀可通过影响细胞周期调控因子的表达而抑制动脉损伤后的内膜增殖反应。

Objective: To investigate the influence of cerivastatin on cell cycle modulatory factors and proliferation response of vessel smooth muscle cell after artery injury in animal model.Methods:24 SD rats were randomly divided into 3 groups:sham operation group,operation group,and cerivastatin group.Each group had 8 rats.Baloon-induced endothelium denudation at thoracic aortae was performed in both the operation group and the cerivastatin group.Three days before and 14 days after the procedure, rats in the cerivastatin group were raised with cerivastatin at the dosage of 0.1 mg/kg·d -1 .All the animals were killed 14 days after procedure,and thoracic Aortae were harvested. We used HE staining and immunohistochemistry staining to measure the protein expressions of cell cycle modulatory factors p27, CDK2, and PCNA. Meanwhile Vessle morphological measurement was taken. Results: Neointima formation was apparent in the arteries from the operation group and was reduced much more in the cerivastatin group( I/M:14.67±3.36 vs 41.50±9.54,P<0.01), while no neointima formation was seen in the sham operation group. Immunohistochemistry staining revealed that p27 protein expressions were high in the middle layer VSMC, while CDK2 and PCNA were not detectable in the sham operation group.p27 protein expressions were high in the the neointima of the operation group and were significantly increased by cerivastatin.In the operation group,the neointima CDK2 and PC-NA were strongly stained and became faint in the cerivastatin group.Conclusion:Cerivastatin surpressed neointima formed after artery injury through up-regulation of p27 and down-regulation of CDK2,PCNA, suggesting that statins are useful in treating vascular proliferate diseases such as AS,post-PTCA restenosis.