辛伐他汀对血小板源生长因子诱导的肺血管平滑肌细胞内粘着斑及肌动蛋白细胞骨架组装的影响及意义  

Effects of Simvastatin on Reorganization of Focal Adhesion and Actin Cytoskeleton in Vascular Smooth Muscle Cells Induced by Platelet-Derived Growth Factor-BB

作　　者：王晓琴[1] 周同甫[1] 刘斌[1] 王娟[1] 刘瀚旻[1] 华益民[1] 

机构地区：[1]四川大学华西第二医院儿科,成都610041

出　　处：《中华妇幼临床医学杂志（电子版）》2008年第5期12-15,共4页Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition)

基　　金：四川省青年科技基金项目(06ZQ026-054)~~

摘　　要：目的观察辛伐他汀（simvastatin）对血小板源生长因子（platelet—derived growth factor—BB，PDGF—BB）诱导的增殖细胞内粘着斑（focal adhesion，FA）蛋白及肌动蛋白细胞骨架动态组装的影响，旨在探讨辛伐他汀抑制血管平滑肌细胞（vascular smooth muscle cell，VSMC）增殖和迁移与细胞骨架变化的关系。方法以体外培养的SD大鼠血管平滑肌细胞为基础，[^3H]—TdR掺入量测定DNA合成，透射电镜观察细胞的表型状态，采用免疫细胞化学和荧光细胞化学法，观察辛伐他汀对血小板源生长因子诱导的肺血管平滑肌细胞增殖细胞内粘着斑蛋白及肌动蛋白细胞骨架组装的影响。结果血小板源生长因子受刺激后（对照组），血管平滑肌细胞[^3H]-TdR掺入量明显增加，电镜示细胞超微结构出现表型变化，血管平滑肌细胞中增殖细胞内粘着斑蛋白中的桩蛋白（paxillin）体积增大、数量增加，血管平滑肌细胞内F—actin数量明显增加，呈纵向平行排列，α—SM—actin体积缩小、数量减少。辛伐他汀可明显抑制这些生物学效应（药物干预组）。结论辛伐他汀可以抑制血小板源生长因子介导的血管平滑肌细胞内增殖细胞内粘着斑蛋白中的桩蛋白，F—actin，α-SM-actin的动态组装，进而发挥抑制血管平滑肌细胞增殖和迁移的能力。Objective To investigate the relationship between proliferation and migration of rats vascular smooth muscle cell（VSMC） and cytoskeleton in vascular smooth muscle cells by observation on effects of simvastatin on reorganization of focal adhesion （FA） and actin cytoskeleton in vascular smooth muscle cells induced by platelet-derived grwoth factor （PDGF-BB）. Methods vascular smooth muscle cells isolated from pulmonary media of SD rats and cultured were adopted. Observation on proliferation and changes of phenotype of vascular smooth muscle cells by using [^3H] thymidine uptake and electron microscopy. The dynamic assemble of focal adhesion and reorganization of the actin cytoskeleton of PDGF- BB-induced vascular smooth muscle cells were studied by immunocytochemistry and Iluorocytochemistry techniques after treated with simvastatin. Results Treatment with PDGF BB for 24 h resulted in a substantial increase in [^3H]thymidine uptake and evident change in phenotype under electron microscopy. There were corresponding increase in the number and size of paxillin-positive focal adhesion and stress fibers and rearrangement of these structures into ordered parallel arrays. Simvastatin could inhibit significantly these biological effects. Conclusion Simvastatin could inhibit the dynamic assemble of focal adhesion and F-actin and α-SM actin in PDGF-BB-induced vascular smooth muscle cells,and then inhibit proliferation and migration of vascular smooth muscle cells.

关 键 词：辛伐他汀 血管平滑肌细胞 细胞骨架 

分 类 号：R96[医药卫生—药理学]