同型半胱氨酸通过下调miR-146促进人主动脉平滑肌细胞增殖.pdf

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目 录

中文摘要···············································································1
英文摘要·················································································3
英文缩写·············································································6
研究论文 同型半胱氨酸通过下调 miR-146 促进人主动脉平滑肌细胞增
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前言···············································································7
材料与方法······································································8
结果··············································································15
附图··········································································17
讨论·············································································21
结论····································································24
参考文献··································································24
综述 同型半胱氨酸和冠状动脉粥样硬化的关系研究······················29
致谢·················································································43
个人简历····································································44
同型半胱氨酸通过下调 miR-146 促进人主动脉平滑肌细胞增殖

摘 要

目的：已证实同型半胱氨酸（homocysteine，Hcy）是动脉粥样硬化
的独立危险因素；且其可通过 PI3K/Akt 信号通路参与细胞增殖的调节。
平滑肌细胞增殖是动脉粥样硬化的主要原因之一。MicroRNA 是一种重要
的参与多种心血管疾病包括动脉粥样硬化的小分子。然而，在同型半胱氨
酸调节通路中，microRNA 在平滑肌细胞增殖中的作用却鲜见报道。在本
研究中，我们以人主动脉平滑肌细胞（Human aortic smooth muscle cell，
HASMC）为模型，通过观察 Hcy 对平滑肌细胞的增殖、miR-146 及 PI3K、
Akt 和 EGFR 的表达，明确 Hcy 对平滑肌细胞作用，以揭示 Hcy 在动脉
粥样硬化发生中的作用机制。
方法：
1. 用含 2%胎牛血清的 DMEM 体外培养原代 HASMC。
2. 将上述培养到第 3~4 代的 HASMC 转移到 96 孔培养板，5×103/孔
培养过夜后，分别用含有 4 种不同浓度（ μM， μM， μM，
μM）的 Hcy 的完全培养基刺激 HASMC 48h，通过 MTS 细胞增殖试验检
测 HASMC 的相对细胞活性。然后通过透射电子显微镜来观察