七叶内酯对大鼠血管平滑肌细胞增殖的抑制及其机制  

Inhibitory Effects of Esculetin on Proliferation of Rat Vascular Smooth Muscle Cells in vitro and the Underlying Mechanism

作　　者：戴榕[1] 郑琼莉[1] 徐全胜[1] 祝炜[1] 

机构地区：[1]武汉市第一医院心内科,武汉430022

出　　处：《华中科技大学学报（医学版）》2009年第2期239-242,共4页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

摘　　要：目的观察七叶内酯(esculetin)对大鼠血管平滑肌细胞(rVSMCs)增殖的影响并探讨其主要机制。方法体外培养rVSMCs,观察不同浓度七叶内酯作用不同时间对rVSMCs增殖的影响。细胞计数及MTT检测rVSMCs的增殖;Western blot检测细胞外调节蛋白激酶(ERK1/2)、蛋白激酶B(Akt)和Caspase-9的表达。结果细胞计数和MTT结果均表明,随着药物浓度的增加(5、25、100μmol/L)和作用时间的延长(24、48、72 h),七叶内酯抑制rVSMCs增殖的作用逐渐增强,与空白对照组相比差异均有统计学意义;各浓度组七叶内酯均能显著抑制Akt、ERK1/2的磷酸化,促进Caspase-9的活化,并呈现出剂量依赖性。结论在一定范围内,七叶内酯可呈剂量和时间依赖性抑制rVSMCs的增殖,其主要机制可能是抑制了Ras-Raf-MEK-ERK/MAPK和Ras-PI3K-Akt信号转导通路。Objective To study the inhibitory effects of esculetin on the proliferation of cultured vascular smooth muscle cells（rVSMCs） in rats and explore the underlying mechanism. Methods Rat VSMCs were cultured in vitro and divided randomly into 4 groups：the blank control group and three esculetin-treated groups （low, moderate and high concentrations） with different action time. Light microscopy was used to observe the morphology of rVSMCs. Cell counting was used to confirm the proliferation of rVSMCs. MTT assay was used to test the activation of rVSMCs. Western blot was used to detect the expression of ERK1/2, and activation of Akt and Caspase-9 in Ras signaling pathway. Results Compared with the blank control group, with the increase of concentrations（5,25,100μmol/L） and prolongation of time（24,48,72 h）, esculetin caused a marked dose-dependent and time-dependent proliferation inhibitory effect on rVSMCs in all other three groups （P〈0.05）. Esculetin could down-regulate the activation of ERK1/2,p-Akt and Caspase-9 in a dose-dependent manner and enhance the activation-of Caspase-9. Conclusion Esculetin can effectively inhibit the proliferation of rVSMCs in vitro in a dose- and time-dependent manner. The antiproliferative effect is mainly mediated by inhibiting the activation of Ras-Raf-MEK-ERK/MAPK and Ras-PI3K- Akt.

关 键 词：七叶内酯 血管平滑肌细胞 细胞增殖 

分 类 号：R329.28[医药卫生—人体解剖和组织胚胎学]