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异常子宫出血患者血管内皮生长因子和平滑肌肌动蛋白表达与子宫内膜血管微血管密度及形态计量分析的评估

Evaluation of the Vascular Endothelial Growth Factor and Smooth Muscle Actin Expression With Microvessel Density and Morphometric Analysis of Endometrial Vessels in Patients With Abnormal Uterine Bleeding.

作者信息

Mahabharathi Kodavali, Sharma Tanya, Mukherjee Soma, Joshi Deepti, Kapoor Neelkamal

机构信息

Pathology and Laboratory Medicine, All India Institute of Medical Sciences, Bhopal, Bhopal, IND.

Obstetrics and Gynaecology, All India Institute of Medical Sciences, Bhopal, Bhopal, IND.

出版信息

Cureus. 2024 Jul 9;16(7):e64125. doi: 10.7759/cureus.64125. eCollection 2024 Jul.

DOI:10.7759/cureus.64125
PMID:39119382
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11306986/
Abstract

BACKGROUND

Abnormal uterine bleeding (AUB) that occurs in a structurally normal uterus with regular menstrual cycles and without other identifiable etiology is often caused by a primary endometrial disorder (AUB-E). Altered vascular morphological changes and expression of markers of angiogenesis have been implicated as an underlying cause in these cases.

OBJECTIVES

The study was conducted to investigate the expression of vascular endothelial growth factor (VEGF) and smooth muscle actin-alpha (SMA-α), and to perform microvessel density (MVD), and morphometric evaluation of endometrial vessels in patients with AUB-E.

MATERIAL AND METHODS

Endometrial biopsies and hysterectomy specimens of 40 patients clinically diagnosed with AUB-E were included in the study with 40 age-matched controls. Immunohistochemistry (IHC) with VEGF and SMA-α was performed, and the expression and staining pattern was recorded as the number of positive vessels per 10 high power fields and intensity scores. Morphometric analysis was performed on CD34 stained sections using Leica Application Suite, version 4.4.0 software (Leica Microsystems, Wetzlar, Germany). MVD was calculated by the vascular hotspot method.

RESULTS

A statistically significant increase in VEGF vessel count (p-value<0.001) and a decline in SMA-α expression (p-value=0.23) was seen in cases as compared to the control group. There was a statistically significant increase in microvessel caliber (p-value=0.01) and MVD (p-value <0.001) in cases as compared to controls.

CONCLUSION

These findings support aberrant vascular proliferation and impaired vessel maturation, contributing to the pathology of AUB-E. Alterations in angiogenesis in these patients reveal potential therapeutic targets for AUB.

摘要

背景

在结构正常、月经周期规律且无其他可识别病因的子宫中发生的异常子宫出血(AUB)通常由原发性子宫内膜疾病(AUB-E)引起。血管形态改变和血管生成标志物的表达变化被认为是这些病例的潜在病因。

目的

本研究旨在调查AUB-E患者血管内皮生长因子(VEGF)和平滑肌肌动蛋白-α(SMA-α)的表达,进行微血管密度(MVD)测定以及子宫内膜血管的形态学评估。

材料与方法

本研究纳入了40例临床诊断为AUB-E的患者的子宫内膜活检和子宫切除标本,并与40例年龄匹配的对照组进行比较。采用VEGF和SMA-α进行免疫组织化学(IHC)检测,记录阳性血管数量(每10个高倍视野)和强度评分作为表达和染色模式。使用Leica Application Suite 4.4.0软件(德国韦茨拉尔徕卡微系统公司)对CD34染色切片进行形态学分析。通过血管热点法计算MVD。

结果

与对照组相比,病例组VEGF血管计数显著增加(p值<0.001),SMA-α表达下降(p值=0.23)。与对照组相比,病例组微血管口径(p值=0.01)和MVD(p值<0.001)有统计学意义的增加。

结论

这些发现支持血管异常增殖和血管成熟受损,这有助于AUB-E的病理过程。这些患者血管生成的改变揭示了AUB潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4749/11306986/6bf1e2e99e57/cureus-0016-00000064125-i04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4749/11306986/a2b389653a9d/cureus-0016-00000064125-i01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4749/11306986/0a9d597fa18b/cureus-0016-00000064125-i02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4749/11306986/ce18f4864c80/cureus-0016-00000064125-i03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4749/11306986/6bf1e2e99e57/cureus-0016-00000064125-i04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4749/11306986/a2b389653a9d/cureus-0016-00000064125-i01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4749/11306986/0a9d597fa18b/cureus-0016-00000064125-i02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4749/11306986/ce18f4864c80/cureus-0016-00000064125-i03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4749/11306986/6bf1e2e99e57/cureus-0016-00000064125-i04.jpg

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本文引用的文献

1
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Hum Reprod Update. 2023 Jul 5;29(4):457-485. doi: 10.1093/humupd/dmad004.
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National survey of abnormal uterine bleeding according to the FIGO classification in Japan.日本基于 FIGO 分类的异常子宫出血的全国性调查。
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Biomarkers in abnormal uterine bleeding†.异常子宫出血的生物标志物†。
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The two FIGO systems for normal and abnormal uterine bleeding symptoms and classification of causes of abnormal uterine bleeding in the reproductive years: 2018 revisions.FIGO 两种正常和异常子宫出血症状系统及其生殖年龄段异常子宫出血病因分类:2018 年修订版。
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Low pericyte coverage of endometrial microvessels in heavy menstrual bleeding correlates with the microvessel expression of VEGF-A.月经过多患者子宫内膜微血管周围细胞覆盖率低与血管内皮生长因子-A(VEGF-A)在微血管中的表达相关。
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Molecular blockade of angiogenic factors: A new therapeutic tool for the treatment of abnormal uterine bleeding.血管生成因子的分子阻断:治疗异常子宫出血的一种新治疗工具。
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The regulation of vascular endothelial growth factor by hypoxia and prostaglandin F₂α during human endometrial repair.缺氧和前列腺素 F₂α 在人子宫内膜修复过程中对血管内皮生长因子的调节。
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