苯磺酸氨氯地平抑制损伤诱导的血管新生内膜形成

Inhibition of Amlodipine besylate on neointimal hyperplasia after balloon injury in rats

目的研究苯磺酸氨氯地平(AM)、阿托伐他汀(AT)单独及联合用药对球囊损伤诱导的血管新生内膜形成影响及机制。方法复制颈总动脉球囊损伤模型,分离颈总动脉制备病理切片,HE染色观察内膜增生情况。免疫组化观察增殖、迁移相关蛋白表达情况。贴块法培养血管平滑肌细胞(VSMC),待生长至70%～80%融合时,分别加入不同浓度苯磺酸氨氯地平,继续孵育24 h,细胞计数及Western印迹法用于分析VSMC增殖活性;伤口愈合实验及明胶酶图实验用于分析VSMC迁移活性。结果 AM抑制球囊损伤诱导的血管新生内膜形成和管腔狭窄,与AT联用增强其抑制效果;AM单独及与AT联合用药抑制球囊损伤诱导的PCNA、KLF5、MMP-9的表达;AM抑制体外培养的VSMC中PCNA、KLF5和c-Jun的表达;降低MMP-2和MMP-9的活性。结论 AM抑制球囊损伤诱导的血管新生内膜形成与其抑制VSMC增殖及迁移活性有关。

Objective To investigate the effects of amlodipine besylate（AM） and atorvastatin（AT） alone and combination of both drugs on the neointimal hyperplasia after balloon injury and the related mechanisms.Methods HE staining and immunohistochemical staining were performed to investigate the effects of AM and AT alone and combination of both drugs on the neointimal hyperplasia after balloon injury.Cell counting analysis and Western blot analysis were performed to analyze the effect of AM on the proliferation of VSMCs induced by serum.Wound healing assays and Zymography analysis were performed to investigate the effect of AM on serum induced migration of VSMCs.Results AM alone and combined with AT inhibited neointimal hyperplasia and the expression of PCNA,KLF5,and MMP-9 in neointima induced by balloon injury.AM inhibited the proliferation and migration of VSMCs induced by serum in vitro.Conclusions AM inhibits neointimal hyperplasia induced by balloon injury by inhibiting the proliferation and migration of VSMCs.