植物雌激素α-玉米赤霉醇对oxLDL诱导人血管内皮细胞ET-1基因表达的影响

发布时间：2018-01-28 01:12

本文关键词： 植物雌激素玉米赤霉 oxLDL 诱导血管内皮细胞 ET-1 基因表达影响　出处：《中国协和医科大学》2005年博士论文　论文类型：学位论文

【摘要】：绝经后妇女应用激素替代疗法(hormone replacement therapy，HRT)能显著降低心血管疾病的发病率。然而，HRT所带来的不良后果如乳腺癌、子宫内膜癌、静脉血栓等，在一定程度上限制了其推广应用。近年来证实植物雌激素大豆异黄酮和木酚素具有一定程度抗动脉粥样硬化(AS)、防治骨质疏松、保护神经系统、防治老年性痴呆等一系列作用，已作为保健品进入市场。然而，我们认为有一种目前尚未被广泛关注的植物雌激素α-玉米赤霉醇(α-Zearalanol，α-ZAL)是值得引起重视的。α-ZAL是一种天然植物激素，具有类雌激素样效应。1996年本课题组首次将其作为植物雌激素引进医学领域，，并开始系统研究抗AS的作用。我们以往的研究从多个层面多次证实α-ZAL的抗AS作用与雌激素相似，但对子宫和乳腺的雌激素样作用比同剂量的雌激素小得多。α-ZAL很可能是比雌激素副作用小而更有应用前景的药物，因而对其抗AS的机理研究更具有重要意义。内皮素—1是目前所知的作用强、持续久的血管收缩肽，它能引起内皮粘附，可以促进血管平滑肌细胞增殖，与AS的发生、发展有密切的关系。 oxLDL在AS的发病机制中具有重要意义。oxLDL所致血管内皮细胞损伤、功能失调是AS的始动环节。oxLDL对内皮细胞的损伤有很多方面，其中它可以诱导内皮细胞ET-1基因表达的异常增高就是非常重要的一个方面，然而对ET-1基因表达异常增高的机理却并不清楚。α-ZAL可以抑制oxLDL诱导的血管内皮细胞ET-1基因表达，其作用机制亦不清楚。本研究的目的是通过ROS信号转导通路探讨oxLDL对血管内皮细胞ET-1基因表达的影响和其分子机制以及α-ZAL
[Abstract]:Postmenopausal women using hormone replacement therapy (hormone replacement, therapy, HRT) can significantly reduce the incidence of cardiovascular disease. However, HRT brings adverse consequences such as breast cancer, endometrial cancer, venous thrombosis, the application was limited to a certain extent. In recent years confirmed that soy isoflavone and lignan element has a certain degree of anti atherosclerosis (AS), the prevention and treatment of osteoporosis, the protection of the nervous system, the treatment of senile dementia and a series of functions, as health care products into the market. However, we think that there is a widespread concern has not yet been phytoestrogen alpha zearalanol (alpha -Zearalanol, alpha -ZAL) is worth attached. A -ZAL is a natural plant hormone, has estrogenic effects in.1996 years the research group for the first time as the introduction of phytoestrogens in medical field, and began to study the anti AS system . our previous studies from multiple levels repeatedly confirm that the anti AS effect of estrogen and -ZAL were similar, but the estrogenic effects on the uterus and breast than the same dose of estrogen is much smaller. A -ZAL is likely to be less side effects than drugs estrogen and more applications, and to study the mechanism of its anti AS it is of great significance.
Endothelin 1 is a highly effective and persistent vasoconstrictor peptide. It can induce endothelial adhesion and promote the proliferation of vascular smooth muscle cells, which is closely related to the occurrence and development of AS.
OxLDL has an important significance of.OxLDL induced vascular endothelial cell injury in the pathogenesis of AS, there are many aspects of.OxLDL dysfunction is the initiating factor of AS damage of endothelial cells, which can induce endothelial cell ET-1 gene expression abnormality is a very important aspect, however, the expression of ET-1 gene abnormality is the mechanism is not clear. The expression of vascular endothelial cells ET-1 gene -ZAL can inhibit oxLDL induced, its mechanism is not clear. The purpose of this study is to investigate the impact of oxLDL ROS signal transduction pathway on the expression of ET-1 gene in vascular endothelial cells and its molecular mechanism and alpha -ZAL

【学位授予单位】：中国协和医科大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R363

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