曲张大隐静脉源性血管平滑肌细胞表型与功能的变化

Alterations in phenotype and function of vascular smooth muscle cells from varicose great saphenous vein

目的:探讨曲张大隐静脉源性血管平滑肌细胞(VSMCs)表型与功能的变化。方法:收集13例曲张大隐静脉(曲张组)与15例正常大隐静脉(正常组)标本,分离和培养两组标本中的VSMCs。检测两组VSMCs的增殖、迁移、黏附、衰老与骨架蛋白表达,以及凋亡相关因子与细胞外基质代谢相关因子的表达。结果:与正常组VSMCs比较,曲张组VSMCs骨架蛋白F-actin表达增加;增殖能力与迁移、黏附、衰老细胞数均明显增加(均P<0.05);促凋亡因子Bas与凋亡执行因子caspase-3的mRNA、蛋白表达明显降低,而凋亡抑制因子Bcl-2的mRNA、蛋白表达明显升高(均P<0.05);基质金属蛋白酶(MMP-2、MMP-9)与基质金属蛋白酶抑制物(TIMP-1、TIMP-1)的mRNA、蛋白表达均明显升高(均P<0.05)。结论:曲张大隐静脉源性VSMCs有明显去分化现象,其增殖和合成能力增强,VSMCs表型和功能的异常可能是静脉曲张发病机制之一。

Objective： To investigate the changes in phenotype and function of vascular smooth muscle cells （VSMCs） from varicose great saphenous vein. Methods： Thirty specimens of varicose great saphenous vein （varicose group） and 15 specimens of normal great saphenous vein （normal group） were collected, and the VSMCs in the two groups of specimens were isolated and cultured. In the two groups of VSMCs, the proliferation, migration, adhesion and aging status and cytoskeletal protein expression, as well as the expressions of apoptosis associated factors and extracellular matrix metabolism associated factors were determined. Results： In VSMCs of varicose group compared with VSMCs of normal group, the expression of cytoskeletal protein F-actin was increased; the proliferative ability and numbers of migrating, adhering, and aging cells were significantly increased （all P〈0.05）; the mRNA and protein expressions of pro-apoptotic factor Bas and apoptotic executioner caspase-3 were significantly decreased, while mRNA and protein expressions of anti-apoptotic factor Bcl-2 was significantly increased （all P〈0.05）; the mRNA and protein expressions of matrix metalloproteinases （MMP-2 and MMP-9） and matrix metalloproteinase inhibitors （TIMP-1 and TIMP-1） were significantly increased （all P〈0.05）. Conclusion： VSMCs from varicose great saphenous vein feature evident dedifferentiation and demonstrate increased proliferative and synthetic capacity. These phenotypic and functional abnormalities in VSMCs may be one of the pathogeneses for varicosity.