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作 者:王欢[1] 刘艳[1] 祝领[1] 王文静[1] 陈方圆[1] 万招飞[1] 周娟[1,2] 袁祖贻[1,2,3]
机构地区:[1]西安交通大学医学院第一附属医院心血管内科,西安市710061 [2]陕西省分子心脏病学重点实验室,西安市710061 [3]西安交通大学医学院环境与疾病相关教育部重点实验室,西安市710061
出 处:《中国分子心脏病学杂志》2013年第4期635-638,共4页Molecular Cardiology of China
基 金:国家重点基础研究发展计划(973计划:No.2012CB51780X);国家自然科学基金资助项目(No.81025002;No.30971219)
摘 要:目的探讨17β-雌二醇对小鼠血管平滑肌细胞(VSMCs)CD36表达的影响及其对肌源性泡沫化细胞产生的作用。方法组织贴块法培养小鼠原代主动脉SMCs;免疫荧光染色观察VSMCs上CD36的表达;17β-雌二醇(1nM~1μM)干预细胞6h~36h,Real-time PCR和Western blot分别检测CD36 mRNA和蛋白的表达变化;酶荧光化学法定量检测17β-雌二醇对ox-LDL诱导的VSMCs内胆固醇蓄积的含量改变。结果 CD36存在于小鼠VSMCs上。17β-雌二醇以浓度依赖和时间依赖方式抑制VSMCs上CD36 mRNA和蛋白的表达(P<0.05),减少ox-LDL诱导的VSMC来源的泡沫细胞内胆固醇酯的蓄积(P<0.05)。非选择性雌激素受体拮抗剂ICI182,780阻断17β-雌二醇对CD36的下调作用及其对胆固醇酯蓄积的影响。结论 17β-雌二醇以雌激素受体依赖的方式,抑制VSMCs上CD36的表达,减轻VSMCs内胆固醇酯蓄积,抑制VSMCs源性的泡沫细胞的形成。Objective The present study was undertaken to investigate the effects of 17 β-estradiol (E2) on CD36 expression and vascular smooth muscle cell (VSMC)-derived foam cell formation. Methods Immunofluorescence microscopy analysis was performed to evaluate localization of CD36 in cultured murine VSMCs. After exposure of VSMCs to different concentrations of E2 (1 nM-1μM) for 24 h or 100 nM E2 for different time (6 h-36 h), the mRNA and protein expression of CD36 was examined by Real-time PCR and Western blot, respectively. The levels of cellular total cholesterol and cholesteryl ester were measured using an enzymatic fluorometric method. Results Immunofluorescence microscopy showed that CD36 was predominantly expressed on the surface of the murine VSMCs. E2 significantly down-regulated CD36 expression in a dose- and time- dependent manner (P 〈0.05). Furthermore, combined treatment with E2 and ox-LDL markedly ameliorated cholesteryl ester accumulation in VSMCs compared with the ox-LDL-treated group (P 〈0.05). However, the inhibitory effects of E2 on CD36 expression and cholesteryl ester accumulation were abolished when non-selective estrogen receptor (ER) antagonist ICI 182,780 was added to E2. Conclusion 1 7β-estradiol decreases CD36 expression and inhibits VSMC-derived foam cell formation through an ER-dependent mechanism.
关 键 词:17Β-雌二醇 血管平滑肌细胞 CD36 泡沫细胞
分 类 号:R543[医药卫生—心血管疾病]
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