骨桥蛋白启动子区域低甲基化与大隐静脉曲张血管平滑肌细胞的表型转化  

Hypomethylation of osteopontin Promoter and phenotype switching of vascular smooth muscle cells in great saphenous varicose veins

作　　者：姜晗[1] 论语 唐佃俊 刘勋[1] 辛世杰[1] 张健[1] 

机构地区：[1]中国医科大学附属第一医院血管甲状腺外科,沈阳110001

出　　处：《中华普通外科杂志》2016年第4期285-288,共4页Chinese Journal of General Surgery

基　　金：辽宁省教育厅重点实验室项目基金资助项目（LS2010172）

摘　　要：目的探讨骨桥蛋白（osteoponti，OPN）启动子区域异常甲基化与大隐静脉曲张血管平滑肌细胞（vascular smooth muscle cell，VSMC）表型转化的关系。方法通过免疫组织化学、Western blot、甲基化特异性PCR及透射电镜，检测抗平滑肌抗体（anti—smooth muscle antibaly，SMA）与OPN在大隐静脉曲张VSMC中表达和OPN的DNA启动子区域甲基化状态：观察静脉曲张新生内膜VSMC的超微结构改变。结果免疫组化结果显示，与正常组相比，静脉曲张组新生内膜VSMC中OPN高表达（曲张组：15．52±0．23，正常组：5．83±0．20，P〈0．01）、SMA呈弱表达（曲张组：37．2±0．8，正常组：53．6±1．5，P〈0．01）；Western blot结果显示，静脉曲张组新生内膜VSMC中OPN表达明显增高（曲张组：1．082±0．006．正常组：0．574±0．009,P〈0．01）。OPN的DNA启动子区域呈低甲基化状态：静脉曲张组新生内膜VSMC粗面内质网、高尔基复合体等细胞器增多。结论静脉曲张VSMC中OPN基因启动子区域的低甲基化可能是诱导OPN高表达的关键因素，提示OPN异常的甲基化状态可能参与了VSMC的表型转换最终导致新生内膜肥厚参与了静脉曲张的发生与发展。Objective To investigate the relationship between abnormal methylation in promoter regions for OPN and VSMC phenotype switching in varicosity. Methods Immunohistochemistry and Western-blot were used to evaluate the expression of SMA and OPN in VSMC. Methylation-specific PCR was used to evaluate the methylation level of OPN in VSMC of vein samples. Uhrastrncture change of VSMC was observed by transmission electron microscope （TEM）. Results Compared to normal vein, OPN in VSMCs were significantly highly expressed, mainly in the neointimal region （ P 〈 0.01 ）. SMA in neointima region was in low expression （ P 〈 0.01 ）. The density of OPN in varicose group was significantly higher （ P 〈 0.01 ）. DNA methylation level of OPN was lower in varicose veins. Conclusions Hypomethylation of the promoter regions for OPN may cause high expression of OPN leading to VSMC phenotype switching and development of varicosity.

关 键 词：静脉曲张 骨桥蛋白质 肌细胞 平滑肌 DNA甲基化 表型转换 

分 类 号：R541.4[医药卫生—心血管疾病]