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抗血管生成治疗对腹膜子宫内膜异位症相关神经纤维的影响。

Effect of antiangiogenic treatment on peritoneal endometriosis-associated nerve fibers.

机构信息

Unidad de Genética, Hospital Universitario y Politécnico La Fe, Valencia, Spain.

出版信息

Fertil Steril. 2012 Nov;98(5):1209-17. doi: 10.1016/j.fertnstert.2012.07.1103. Epub 2012 Aug 21.

Abstract

OBJECTIVE

To investigate the effect of antiangiogenic treatment on experimental endometriotic lesion nerve fibers.

DESIGN

Heterologous mouse model of endometriosis.

SETTING

University Institute IVI, University Hospital La Fe.

ANIMAL(S): Ovariectomized nude mice (n = 16) receiving human endometrial fragments from oocyte donors (n = 4).

INTERVENTION(S): Endometrium fragments stuck in the peritoneum of 5-week-old female nude mice treated with vehicle (n = 8) and antiangiogenic agent cabergoline (n = 8; Cb(2,) 0.05 mg/kg/day) for 14 days.

MAIN OUTCOME MEASURE(S): Immunofluorescence analysis of von-Willebrand factor (vWF) and vascular smooth muscle cells (αSMA) for evaluating the number of immature blood vessels (IBV) and microvascular density (MVD); immunochemical analysis of protein-gene product 9.5 (PGP 9.5) to assess nerve fibers density (NFD), and blue toluidine staining to confirm presence of mast cells and macrophages in endometriotic lesions.

RESULT(S): All the results were quantified by morphometric techniques. The IBV, NFD, and number of macrophages and mast cells were statistically significantly decreased in the Cb2-treated group when compared with controls.

CONCLUSION(S): Antiangiogenic treatment statistically significantly diminishes new blood vessel formation after macrophage, mast cell, and nerve fiber reduction, providing a rationale to test antiangiogenic agents as a novel therapeutic approach to severe pelvic pain associated with human peritoneal endometriosis.

摘要

目的

研究抗血管生成治疗对实验性子宫内膜异位症病灶神经纤维的影响。

设计

子宫内膜异位症的异种小鼠模型。

地点

IVI 大学研究所,La Fe 大学医院。

动物

接受卵母细胞供体人子宫内膜碎片的去卵巢裸鼠(n = 16)(n = 4)。

干预

将子宫内膜碎片贴在 5 周龄雌性裸鼠的腹膜上,用载体(n = 8)和抗血管生成剂卡麦角林(n = 8;Cb(2,) 0.05 mg/kg/天)治疗 14 天。

主要观察指标

von-Willebrand 因子(vWF)和血管平滑肌细胞(αSMA)的免疫荧光分析,用于评估不成熟血管(IBV)和微血管密度(MVD)的数量;蛋白基因产物 9.5(PGP 9.5)的免疫化学分析,以评估神经纤维密度(NFD),以及甲苯胺蓝染色以确认子宫内膜异位症病灶中肥大细胞和巨噬细胞的存在。

结果

所有结果均通过形态计量技术进行定量。与对照组相比,Cb2 治疗组的 IBV、NFD、巨噬细胞和肥大细胞数量均显著减少。

结论

抗血管生成治疗可显著减少新血管形成,同时减少巨噬细胞、肥大细胞和神经纤维,为抗血管生成剂作为治疗与人类腹膜子宫内膜异位症相关的严重盆腔疼痛的新疗法提供了依据。

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