中文摘要：

目的探讨在胰岛素诱导动脉粥样硬化发生的过程中,雌激素受体α（estrogen receptorα,ER-α）的作用。方法 18周龄Apoe/Lepr基因双敲小鼠按随机数字表法分为对照组和实验组（4 IU胰岛素组）,每组4只。HE染色及免疫组化观察小鼠血管动脉斑块形成及α-平滑肌肌动蛋白（smooth muscle actin-α,α-SMA）、ER-α的表达。2用胰岛素及甲基化转移酶抑制剂干预大鼠血管平滑肌细胞,采用RT-PCR及Western blot检测DNA甲基化酶、ER-α的表达,划痕实验及流式细胞仪检测ER-α对血管平滑肌细胞增殖的影响。结果 1实验组小鼠血管出现动脉斑块,免疫组化结果显示α-SMA、ER-α表达降低（P〈0.05）。2与对照组比较,胰岛素处理后血管平滑肌细胞中DNA甲基化酶的mRNA与蛋白表达升高（P〈0.01）,而ER-α表达下降（P〈0.01）,甲基化酶抑制剂可以消除这种差异,高表达ER-α后,划痕实验及流式细胞仪检测结果显示血管平滑肌细胞增殖减慢（P〈0.05）。结论胰岛素通过促进DNA甲基化酶的表达,诱导ER-α基因甲基化,使ER-α表达下降,最终导致动脉粥样硬化的发生。

英文摘要：

Objective To determine the role of estrogen receptor α（ ER-α） during the process of insulin-induced atherosclerosis. Methods Eight-week-old Apoe / Lepr double knockout mice（ n = 8） were randomly divided to control group（ N） and experimental group（ INS,4 IU,intra-peritoneal injection,5 times per week,for 3 months）. The vascular atherosclerotic plaques and expression levels of ER-α,alpha smooth muscle actin（ α-SMA） were detected by hematoxylin-eosin（ HE） staining and immunohistochemical analysis.Insulin was applied to intervene rat vascular smooth muscle cells（ VSMCs）,and the expression levels of DNA methyltransferase 3a（ DNMT3a） and ER-α were assessed by RT-PCR and Western blotting. Furthermore,wound-healing assay and flow cytometry were used to detect the effect of ER-α on the proliferation and migration in VSMCs. Results The experimental mice showed atherosclerosis plaques and lower expression of ER-α and α-SMA than the control group（ P 〈 0. 05）. The mRNA and protein expression of ER-α was significantly lower,while that of DNMT3 a was obviously higher in the experimental group than the control group（ P 〈 0. 01）,but 5-Aza-2’-deoxycytidine（ 5-Aza） could eliminate these differences（ P 〈 0. 05）.Wound-healing assay and flow cytometry showed that ER-α inhibited the proliferation and migration of VSMCs（ P 〈 0. 05）. Conclusion By up-regulating the expression of DNMT3 a and inducing the methylation of ER-α,insulin suppresses the expression of ER-α and then leads the formation of atherosclerosis.