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选择性环氧化酶-2 抑制剂通过抗血管生成作用抑制子宫内膜异位症在大鼠模型中的生长。

A selective cyclooxygenase-2 inhibitor suppresses the growth of endometriosis with an antiangiogenic effect in a rat model.

机构信息

Programa de Pesquisa em Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Cidade Universitária-Ilha do Fundão, Rio de Janeiro, Brazil.

出版信息

Fertil Steril. 2010 May 15;93(8):2674-9. doi: 10.1016/j.fertnstert.2009.11.037. Epub 2010 Jan 13.

Abstract

OBJECTIVE

To analyze the antiangiogenic effects of the selective cyclooxygenase-2 (COX-2) inhibitor parecoxib on the growth of endometrial implants in a rat model of peritoneal endometriosis.

DESIGN

Pharmacologic interventions in an experimental model of peritoneal endometriosis.

SETTING

Research laboratory in the Federal University of Rio de Janeiro.

ANIMAL(S): Twenty female Sprague-Dawley rats with experimentally induced endometriosis.

INTERVENTION(S): After implantation and establishment of autologous endometrium onto the peritoneum abdominal wall, rats were randomized into groups and treated with parecoxib or the vehicle by IM injection for 30 days.

MAIN OUTCOME MEASURE(S): Vascular density, the expression of vascular endothelial growth factor (VEGF) and its receptor Flk-1, the distribution of activated macrophages, the expression of COX-2, and the prostaglandin concentration in the endometriotic lesions treated with parecoxib were analyzed.

RESULT(S): The treatment significantly decreased the implant size, and histologic examination indicated mostly atrophy and regression. A reduction in microvessel density and in the number of macrophages, associated with decreased expression of VEGF and Flk-1, also were observed. The treatment group showed a low concentration of prostaglandin E(2).

CONCLUSION(S): These results suggest that the use of COX-2 selective inhibitors could be effective to suppress the establishment and growth of endometriosis, partially through their antiangiogenic activity.

摘要

目的

分析选择性环氧化酶-2(COX-2)抑制剂帕瑞昔布对腹膜子宫内膜异位症大鼠模型中子宫内膜种植体生长的抗血管生成作用。

设计

在腹膜子宫内膜异位症的实验模型中进行药理学干预。

地点

里约热内卢联邦大学的研究实验室。

动物

20 只雌性 Sprague-Dawley 大鼠,经实验诱导患有子宫内膜异位症。

干预

在将自体子宫内膜植入腹壁腹膜后,大鼠被随机分为两组,通过肌内注射接受帕瑞昔布或载体治疗 30 天。

主要观察指标

血管密度、血管内皮生长因子(VEGF)及其受体 Flk-1 的表达、活化巨噬细胞的分布、COX-2 的表达以及接受帕瑞昔布治疗的异位病灶中的前列腺素浓度。

结果

治疗显著减小了种植体的大小,组织学检查表明主要是萎缩和退化。还观察到微血管密度和巨噬细胞数量减少,同时 VEGF 和 Flk-1 的表达降低。治疗组前列腺素 E(2)浓度较低。

结论

这些结果表明,使用 COX-2 选择性抑制剂可能有效抑制子宫内膜异位症的建立和生长,部分通过其抗血管生成活性。

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