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反复给予普萘洛尔对手术诱导的大鼠子宫内膜异位症模型的影响。

Effects of repeated propranolol administration in a rat model of surgically induced endometriosis.

作者信息

Uzunlar Ozlem, Ozyer Sebnem, Engin-Ustun Yaprak, Moraloglu Ozlem, Gulerman H Cavidan, Caydere Muzaffer, Keskin Senem M, Mollamahmutoglu Leyla

机构信息

Department of Obstetrics and Gynecology, Zekai Tahir Burak Women's Health Education and Research Hospital, Ankara, Turkey.

Department of Obstetrics and Gynecology, Zekai Tahir Burak Women's Health Education and Research Hospital, Ankara, Turkey.

出版信息

Eur J Obstet Gynecol Reprod Biol. 2014 Nov;182:167-71. doi: 10.1016/j.ejogrb.2014.09.025. Epub 2014 Sep 22.

Abstract

OBJECTIVES

To determine whether propranolol has an inhibitory effect on the angiogenesis of endometriosis in an experimental rat model or not.

STUDY DESIGN

This was an experimental animal model study. Twenty-four female Wistar albino rats (200-250 g) were used to create a model for surgical induction of endometriosis. Two rats died during the surgeries. The rats were randomly divided into treatment (n=11) and control groups (n=10), which were treated with daily intraperitoneal propranolol (10 mg/kg) and saline (2 mL), respectively. Study duration was 8 weeks. The volumes and histopathological findings of the implants, and immunochemistry for vascular endothelial growth factor (VEGF), metalloproteinase (MMP)-2, and MMP-9 were evaluated.

RESULTS

Viable endometriotic implants were created in all animals. In the propranolol-treated group, the mean implant volume significantly decreased after treatment (142.5 vs. 32.1 mm(3), respectively; p=0.008), while the mean implant volume significantly increased in the control group (141.0 vs. 174.2 mm(3), respectively; p=0.009). There were also significant reductions in VEGF immunoreactivity scores and both stroma and epithelium MMP-2 and MMP-9 immunoreactivity scores in the propranolol-treated group compared with the control group (p<0.005 for all scores).

CONCLUSIONS

Propranolol may suppress endometrial tissue by its antiangiogenic activity through inhibitory actions on VEGF, MMP-2, and MMP-9. Therefore, propranolol is a promising candidate drug for effective treatment of patients with endometriosis, which needs to be confirmed with further studies.

摘要

目的

确定普萘洛尔在实验性大鼠模型中是否对子宫内膜异位症的血管生成具有抑制作用。

研究设计

这是一项实验动物模型研究。使用24只雌性Wistar白化大鼠(200 - 250克)建立手术诱导子宫内膜异位症的模型。两只大鼠在手术过程中死亡。大鼠被随机分为治疗组(n = 11)和对照组(n = 10),分别每日腹腔注射普萘洛尔(10毫克/千克)和生理盐水(2毫升)。研究持续时间为8周。评估植入物的体积和组织病理学发现,以及血管内皮生长因子(VEGF)、金属蛋白酶(MMP)-2和MMP-9的免疫化学情况。

结果

所有动物均成功创建了存活的子宫内膜异位植入物。在普萘洛尔治疗组中,治疗后植入物的平均体积显著减小(分别为142.5与32.1立方毫米;p = 0.008),而对照组中植入物的平均体积显著增加(分别为141.0与174.2立方毫米;p = 0.009)。与对照组相比,普萘洛尔治疗组的VEGF免疫反应性评分以及基质和上皮MMP-2和MMP-9免疫反应性评分也均显著降低(所有评分p < 0.005)。

结论

普萘洛尔可能通过对VEGF、MMP-2和MMP-9的抑制作用,以其抗血管生成活性抑制子宫内膜组织。因此,普萘洛尔是有效治疗子宫内膜异位症患者的一种有前景的候选药物,这需要进一步研究来证实。

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