白杨素抑制血小板源性生长因子诱导的血管平滑肌细胞迁移和表型转换  

Effects of Chrysin on Platelet Derived Growth Factor- induced Migration and Phenotypic Switching of Vascular Smooth Muscle Cells

作　　者：严玲[1] 廖正凯[2] 关红菁[1] 唐其柱[1] 

机构地区：[1]武汉大学人民医院心内科、武汉大学心血管病研究所、心血管病湖北省重点实验室,430060 [2]武汉大学中南医院放化疗科,430071

出　　处：《医学研究杂志》2016年第1期25-28,共4页Journal of Medical Research

基　　金：国家自然科学基金资助项目(81000095,30800278,81530012);高等学校新教师基金资助项目(200804861048)

摘　　要：目的研究白杨素对血小板源性生长因子(PDGF)-BB诱导的血管平滑肌细胞(VSMCs)迁移和表型转换的影响及可能的分子机制。方法采用Transwell小室法评价白杨素对PDGF-BB诱导的VSMCs迁移的影响,Western blot法测定收缩型VSMCs标志蛋白:α-平滑肌肌动蛋白(α-SMA)、平滑肌22α(SM22α)和结蛋白的表达水平,以及AKT和糖原合酶激酶(GSK)3β的总蛋白和磷酸化蛋白水平。结果 20ng/ml PDGF-BB明显促进VSMCs迁移,而12.5μmol/L白杨素预处理能显著抑制PDGF-BB诱导的VSMCs迁移;20ng/ml PDGF-BB显著降低VSMCs中α-SMA、SM22α和结蛋白的蛋白表达水平,而12.5μmol/L白杨素预处理能逆转这些标志蛋白的下调;20ng/ml PDGF-BB显著升高VSMCs中AKT和GSK3β磷酸化表达水平,12.5μmol/L白杨素预处理几乎完全阻断PDGF-BB诱导的这些信号分子的磷酸化。结论白杨素显著抑制PDGF-BB诱导的VSMCs迁移,并能阻止PDGF-BB诱导的VSMCs收缩表型向合成表型转换,其机制可能部分与抑制AKT信号通路活化有关。Objective To investigate the effects of ehrysin on the migration and phenotypie switching of vascular smooth muscle cells （VSMCs） induced by platelet derived growth factor （PDGF） - BB and the possible molecular mechanism. Methods Migration of VSMCs was determined by transwell assay. Western blot was performed using antibodies against the following contractile VSMC markers： α - smooth muscle aetin （ α - SMA） , smooth muscle 22α （SM22α） , and desmin. Western blot was also carried out to evaluate total and phosphorylated protein levels of AKT, and glycogen synthase kinase 3β （GSK3β）. Results Treatment of VSMCs with PDGF - BB （20ng/mL） significantly increased the number of migrated cells. However, 12.5μLmol/L ehrysin pretreatmenl markedly blocked this migration response. The expression levels of α - SMA, SM22α and desmin were significantly reduced in PDGF - BB - stimulated VSMCs. In contrast, 12.5μmol/L ehrysin pretreatment reversed the downregulation of these markers. PDGF -BB induced a significant increase in the levels of phosphorylatcd AKT, and GSK3β. However, the PDGF - BB - induced activation of these signaling molecules was almost completely blocked by 12.5μmol/L ehrysin pretreatment. Conclusion Chrysin can suppress the migration of VSMCs induced by PDGF - BB and prevent the phenotypic switching of VSMCs from a ＂contractile＂ to a ＂synthetic＂ state in response to PDGF - BB. These beneficial effects on VSMCs were at least partly mediated by the inhibition of the AKT signaling pathways.

关 键 词：白杨素 血小板源性生长因子 血管平滑肌细胞 细胞运动 表型转换 

分 类 号：R5[医药卫生—内科学]