中文摘要：

目的探讨雌激素诱导合成型血管平滑肌细胞（VSMCs）凋亡的分子机制。方法体外培养第3代的雌性大鼠VSMCs分为3组：17β-雌二醇（E2）组、p38通路阻断（SB＋E2）组和对照组。药物处理72h后，ELISA法检测细胞内核小体以检测VSMCs凋亡率，Western blotting检测p38总蛋白、磷酸化p38（p-p38）的变化及肌细胞增强因子-2（MEF2）的表达，免疫组织化学染色确认MEF2的定位和表达。结果ELISA检测显示，E2组VSMCs凋亡率明显高于对照组，而SB＋E2组无明显变化。Western blotting显示，E2组p38、p-p38和MEF2均明显增高，而SB＋E2组p38表达无明显变化，p-p38和MEF2明显降低。免疫组织化学染色显示，MEF2主要定位于细胞核，各组表达水平与Western blotting结果一致。结论雌激素可能通过激活p38通路上调MEF2的表达，诱导VSMCs凋亡。

英文摘要：

Objective To explore the underlying molecular mechanisms of estrogen induced apoptosis of synthetic vascular smooth muscle cells （VSMCs）. Methods Cultured VSMCs on passage 3 were divided into three groups： 17β-estradiol （ E2 ） group, p38 inhibitor group （ SB ＋ E2 ） and control group. With treatment for 72 hours, the apoptosis of cells was quantified by measuring the intracellular nucleosomes with ELISA; expressions of total p38, phospho-p38 and myocyte enhancer factor-2 （MEF2） were analyzed by Western blotting, with a contlrmative immunohistochemical staining for MEF2. Results Compared with that of control cells, the rate of apoptosis in VSMCs grown in E2 was significantly increased, with up-regulations of total p38, phospho-p38 and MEF2. These effects of E2 were blocked in SB ＋ E2 group in which the rate of cell apoptosis and expression of p38 had no obvious change compared with that of control group, while the expression of p-p38 and MEF2 was decreased. Immunohistochemical staining showed that MEF2 was mainly located in cellular nucleus, and its expression was increased in E2 group but decreased in SB ＋ E2 group. Conclusion Estrogen may induce apoptosis of synthetic VSMCs through p38 pathwaydependent up-regulation of MEF2.