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孟鲁司特对大鼠实验性诱导子宫内膜异位症模型中子宫内膜植入物的消退是否有效?

Is montelukast effective in regression of endometrial implants in an experimentally induced endometriosis model in rats?

作者信息

Kiykac Altinbas Sadiman, Tapisiz Omer Lutfi, Cavkaytar Sabri, Simsek Gulcin, Oguztuzun Serpil, Goktolga Umit

机构信息

Etlik Zubeyde Hanım Women's Health Training and Research Hospital, Department of Obstetrics and Gynecology, Ankara, Turkey.

Etlik Zubeyde Hanım Women's Health Training and Research Hospital, Department of Obstetrics and Gynecology, Ankara, Turkey.

出版信息

Eur J Obstet Gynecol Reprod Biol. 2015 Jan;184:7-12. doi: 10.1016/j.ejogrb.2014.10.026. Epub 2014 Oct 30.

Abstract

OBJECTIVE

Montelukast, a selective antagonist of Type 1 cysteinyl leukotriene receptors (CysLT1Rs), antagonizes the proinflammatory and proasthmatic activities of CysLT1Rs. We investigated the effect of montelukast on a surgically induced endometriosis rat model.

STUDY DESIGN

Thirty-two sexually mature, cycling, female Wistar-Albino rats, in which endometriotic implants were surgically induced, were randomly divided into three groups. Group I [Montelukast (M), 10 rats)] was given 1.6 mg/kg/day of oral montelukast sodium. Group II [Leuprolide acetate (L), 11 rats] was given 1 mg/kg single dose of s.c.leuprolide acetate. Group III [Control (C), 11 rats] received saline solution through an orogastric tube and served as controls. After a 3-weeks medication, the rats were sacrificed to investigate the endometriotic implants for size and morphological and histological characteristics, including immunoreactivity of MMP-2 and VEGF.

RESULTS

The mean area of implants decreased from 48.2 ± 24.7 to 29.3 ± 15.8mm(2) in Group I (M) (P = 0.008) and from 62 ± 32.1 to 39.9 ± 18.1mm(2) in Group II (L) (P=0.003). In Group III (C), the mean area increased from 41.1 ± 31.1 to 60.4 ± 37.1mm(2) (P = 0.025). Histopathological analysis showed statistically significant lower scores in rats treated with montelukast compared to leuprolide and controls. MMP H scores were not different between the groups in both epithelial and stromal MMP-2 immunostaining. VEGF H scores were statistically lower in Group 1 (M) in epithelial VEGF immunostaining when compared to Group II (L) and Group III (C) (P=0.006).

CONCLUSION(S): Montelukast may effectively cause a significant decrease in the area of endometriotic implants.

摘要

目的

孟鲁司特是1型半胱氨酰白三烯受体(CysLT1Rs)的选择性拮抗剂,可拮抗CysLT1Rs的促炎和促哮喘活性。我们研究了孟鲁司特对手术诱导的子宫内膜异位症大鼠模型的影响。

研究设计

32只性成熟、处于发情周期的雌性Wistar-白化大鼠,通过手术诱导产生子宫内膜异位植入物,随机分为三组。第一组[孟鲁司特(M),10只大鼠]给予1.6mg/kg/天的口服孟鲁司特钠。第二组[醋酸亮丙瑞林(L),11只大鼠]给予1mg/kg单剂量的皮下注射醋酸亮丙瑞林。第三组[对照组(C),11只大鼠]通过口胃管给予生理盐水作为对照。用药3周后,处死大鼠,研究子宫内膜异位植入物的大小、形态和组织学特征,包括MMP-2和VEGF的免疫反应性。

结果

第一组(M)植入物的平均面积从48.2±24.7降至29.3±15.8mm²(P = 0.008),第二组(L)从62±32.1降至39.9±18.1mm²(P = 0.003)。第三组(C)的平均面积从41.1±31.1增加到60.4±37.1mm²(P = 0.025)。组织病理学分析显示,与亮丙瑞林和对照组相比,孟鲁司特治疗的大鼠得分在统计学上显著更低。在上皮和基质MMP-2免疫染色中,各组之间的MMP H评分没有差异。与第二组(L)和第三组(C)相比,第一组(M)上皮VEGF免疫染色中的VEGF H评分在统计学上更低(P = 0.006)。

结论

孟鲁司特可能有效地使子宫内膜异位植入物的面积显著减小。

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