脂氧素抑制子宫内膜异位症的分子机制

发布时间：2018-04-23 11:44

  本文选题：脂氧素 + 子宫内膜异位症　； 参考：《厦门大学》2014年硕士论文

【摘要】：目的：研究脂氧素A4(lipoxin A,LXA4)与雌激素受体(estrogen receptor,ER)、孕激素受体(progestrone receptor, PR)之间的关系,探索LXA4对ER、PR表达的影响及LXA4对ER-p38丝裂原活化蛋白激酶(p38mitogen-activated protein kinase, p38MAPK)串话通路的调节作用。 方法：采用酶联免疫吸附试验、实时荧光定量PCR和免疫组织化学法检测内异症患者及正常妇女中LXA、ER、PR的表达。通过实时荧光定量PCR检测ER、PR、肿瘤坏死因子-a(tumor necrosis factor-alpha, TNF-a)、白介素-6(interleukin-6,IL-6)的mRNA表达。利用western blot和免疫组织化学法检测p38MAPK的磷酸化。采用荧光素酶报告基因测定雌激素反应元件(estrogen response element, ERE)的转录活性。利用MTS法和EdU法检测LXA4对子宫内膜异位间质细胞(endometriotic stromal cells, ESCs)增殖的影响。 结果：在正常子宫内膜组织中,ERa和ERβmRNA均存在周期性变化规律,而在异位病灶中,ERa和ERβmRNA在不同月经周期中的表达情况无明显改变,失去周期性变化规律。LXA、ERa和PR在内异症患者病灶组织中低表达,ERβ在异位病灶组织中显著高表达。外源性LXA4可以明显上调ERβ的表达,而ERp特异性激动剂DPN可以抑制p38MAPK磷酸化。同时LXA4可以抑制雌二醇(estradiol,E2)诱导的p38MAPK的磷酸化及其下游细胞炎性因子TNF-a和IL-6的表达,抑制E2诱导的ESCs的增殖。 结论：LXA4可以促进ESCs中ERβ的表达,并很可能通过ERβ抑制E2诱导的p38MAPK磷酸化,从而抑制异位病灶的生长。
[Abstract]:Aim: to investigate the relationship between lipoxygenin A4(lipoxin Agna _ 4 and estrogen receptor estrogen receptor ERA, progesterone receptor progestrone receptor, and to explore the effect of LXA4 on ERP PR expression and the regulation of LXA4 on ER-p38 mitogen-activated protein kinase (p38MAPK) crosstalk pathway. Methods: enzyme linked immunosorbent assay (Elisa), real-time fluorescence quantitative PCR and immunohistochemistry were used to detect the expression of LXA ERP PR in patients with endometriosis and normal women. The mRNA expression of ERP, tumor necrosis factor-alpha, TNF-a, interleukin-6 interleukin-6 (IL-6) was detected by real-time fluorescence quantitative PCR. Western blot and immunohistochemistry were used to detect the phosphorylation of p38MAPK. The transcriptional activity of estrogen response element (ERE) was determined by luciferase reporter gene. The effects of LXA4 on the proliferation of endometrial stromal stromal cells (ESCs) were detected by MTS and EdU. Results: in normal endometrium, there were periodic changes of ERa and ER 尾 mRNA, but there was no significant change in the expression of ERa and ER 尾 mRNA in ectopic lesions in different menstrual cycles. The expression of ER 尾 was significantly higher in ectopic lesions than that in patients with LXA ERa and PR. Exogenous LXA4 could significantly up-regulate the expression of ER 尾, while ERp specific agonist DPN could inhibit p38MAPK phosphorylation. At the same time, LXA4 could inhibit the phosphorylation of p38MAPK induced by estradiolium E _ 2 and the expression of TNF-a and IL-6, as well as the proliferation of ESCs induced by E _ 2. Conclusion: the expression of ER 尾 in ESCs can be promoted by WLXA4, and it is possible that ER 尾 inhibits the p38MAPK phosphorylation induced by E2 and thus inhibits the growth of ectopic lesions.
【学位授予单位】：厦门大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R711.71

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