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腹腔液对子宫内膜细胞培养中血管生成和蛋白水解因子表达的影响。

Influence of peritoneal fluid on the expression of angiogenic and proteolytic factors in cultures of endometrial cells from women with endometriosis.

机构信息

Research Center, Hospital Universitario La Fe, Valencia, Spain.

出版信息

Hum Reprod. 2010 Feb;25(2):398-405. doi: 10.1093/humrep/dep419. Epub 2009 Nov 26.

Abstract

BACKGROUND

Endometriosis, defined as the presence of endometrium outside the uterus, is one of the most frequent benign gynaecological diseases. It has been suggested that both endometrial and peritoneal factors, related to angiogenesis and proteolysis, can be implicated in this disease. The aim of this study was to evaluate the influence of peritoneal fluid on the expression of angiogenic and proteolytic factors in cultures of endometrial cells from women with and without endometriosis.

METHODS

Endometrial cells were isolated, cultured and treated with endometriotic or normal peritoneal fluid. Vascular endothelial growth factor-A (VEGF-A), urokinase plasminogen activator (uPA), matrix metalloproteinase-3 (MMP-3) and their inhibitors including thrombospondin-1, plasminogen activator inhibitor-1 and MMP inhibitor type 1 (TIMP-1) mRNA levels were evaluated by quantitative RT-PCR, and protein levels were quantified by ELISA.

RESULTS

Peritoneal fluid from women with endometriosis induced an increase in VEGF-A and uPA protein and VEGF-A mRNA and uPA mRNA levels in endometrial cell culture from women with (P < 0.01) and without endometriosis (P < 0.05). The highest levels of VEGF-A and uPA were observed in endometrial cell cultures from patients with endometriosis and treated with peritoneal fluid from women with endometriosis.

CONCLUSIONS

Peritoneal fluid from women with endometriosis induced more VEGF and uPA expression in endometrial cell culture from women with endometriosis than did normal peritoneal fluid. Endometrial-peritoneal interactions increased angiogenic and proteolytic factors in endometrial cells, which could contribute to the development of endometriotic lesions.

摘要

背景

子宫内膜异位症是指子宫内膜出现在子宫以外的位置,是最常见的妇科良性疾病之一。有研究认为,与血管生成和蛋白水解有关的子宫内膜和腹膜因素可能与这种疾病有关。本研究旨在评估腹腔液对子宫内膜异位症和非子宫内膜异位症患者子宫内膜细胞培养中血管生成和蛋白水解因子表达的影响。

方法

分离、培养子宫内膜细胞,并与子宫内膜异位症或正常腹膜液处理。采用实时定量 RT-PCR 检测血管内皮生长因子 A(VEGF-A)、尿激酶型纤溶酶原激活物(uPA)、基质金属蛋白酶-3(MMP-3)及其抑制剂包括血小板反应蛋白-1(TSP-1)、纤溶酶原激活物抑制剂-1(PAI-1)和基质金属蛋白酶抑制剂-1(TIMP-1)的 mRNA 水平,采用 ELISA 法检测蛋白水平。

结果

子宫内膜异位症患者的腹腔液诱导子宫内膜异位症和非子宫内膜异位症患者子宫内膜细胞培养中 VEGF-A 和 uPA 蛋白和 VEGF-A mRNA 和 uPA mRNA 水平升高(P < 0.01)。在子宫内膜异位症患者的子宫内膜细胞培养中,与子宫内膜异位症患者的腹腔液相比,正常腹腔液诱导的 VEGF-A 和 uPA 水平较低。

结论

子宫内膜异位症患者的腹腔液在子宫内膜异位症患者的子宫内膜细胞培养中诱导更高水平的 VEGF 和 uPA 表达,而非正常腹腔液。子宫内膜-腹膜相互作用增加了子宫内膜细胞中血管生成和蛋白水解因子的表达,这可能有助于子宫内膜异位症病变的发展。

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