应激在子宫内膜异位症发生发展中的作用

项目名称： 应激在子宫内膜异位症发生发展中的作用

项目编号： No.81471434

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 郭孙伟

作者单位： 复旦大学

项目金额： 74万元

中文摘要： 慢性(精神)应激对健康的不良影响已为科学界公认。众多证据表明：子宫内膜异位症（内异症）患者由于饱受诸如慢性盆腔痛及不孕等症状的困扰，生活质量及工作效率下降，焦虑水平及自身感受到的应激水平上升。我们的前期研究表明：小鼠在手术建模1天后人为进行应激，其病灶相对于无应激组增加了近一倍，而内异症患者异位内膜中β2-肾上腺素受体的表达亦显著升高。但是，应激对内异症发生发展中作用的研究在国内外几乎是一个空白。本课题旨在研究应激激素在异位内膜细胞中对细胞增殖、侵袭、新生血管形成、炎症因子产生的分子生物学机制。此外，通过体内动物模型实验，进一步验证哪些肾上腺素受体在起作用，并确定是否可以通过药物手段（如β-阻断剂）干扰肾上腺素受体以期降低甚至去除应激对内异症的促进作用。我们相信，阐明应激在内异症发生发展中起重要促进作用的机制，可以进一步认识内异症的发生发展机制，为开发更有效的治疗内异症的药物奠定基础。

中文关键词： 子宫内膜异位症；发病机制；应激；细胞凋亡；血管生成

英文摘要： The negative impact of chronic psychological stress on health is now well documented. Mounting evidence indicates that symptoms such as chronic, incapacitating pelvic pain and infertility negatively and substantially impact the physical and mental health status, health-related quality of life, and productivity on women with endometriosis. They are also reported to have elevated anxiety levels, elevated perceived stress levels and reduced quality of life. We preliminary data suggest that mice that were under stress one day after surgical induction of endometriosis for 2 weeks had their lesion size nearly doubled than those that received regular handling (no stress). In addition, β2-adrenergic receptor is found to be overexpressed in the ectopic endometrium in women with endometriosis. Despite these findings, the role of stress on the development of endometriosis has received scant attention. The purpose of this project is to investigate the impact of stress hormones, mostly epinephrine and norepinephrine, on cellular proliferation, invasiveness, angiogenesis, and the production of proinflammatory cytokines in endometriotic cells. In addition, the involvement of specific adrenergic receptors in endometriosis development will be validated through mouse models, which also will be used to determine as whether intervention through pharmacological means would be of any utility in mitigating or even eliminating the promoting effect of stress. We believe that a better understanding as how stress impacts on the development of endometriosis would shed new light into the pathogenesis of endometriosis, helping to develop more efficacious therapeutics for endometriosis.

英文关键词： endometriosis;pathogenesis;stress;apoptosis;angiogenesis