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儿童婴儿血管瘤普萘洛尔治疗过程中血清血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF)的浓度:我们是否更接近了解普萘洛尔对血管瘤的作用机制?

Serum concentrations of VEGF and bFGF in the course of propranolol therapy of infantile hemangioma in children: Are we closer to understand the mechanism of action of propranolol on hemangiomas?

作者信息

Babiak-Choroszczak Lidia, Giżewska-Kacprzak Kaja, Gawrych Elżbieta, Fischer Katarzyna, Walecka Anna, Puchalska-Niedbał Lidia, Rajewska-Majchrzak Justyna, Bagłaj Maciej

机构信息

Department of Pediatric and Oncological Surgery, Pomeranian Medical University in Szczecin, Poland.

Independent Laboratory of Rheumatic Diagnostics, Pomeranian Medical University in Szczecin, Poland.

出版信息

Adv Clin Exp Med. 2018 May;27(5):703-710. doi: 10.17219/acem/84800.

Abstract

BACKGROUND

Propranolol has become the treatment of choice for infantile hemangiomas (IH). Neither the pathogenesis of IH nor the mechanism of action of propranolol on them are well understood. Possible explanations include the inhibition of angiogenesis by decreasing vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), induction of vascular endothelial cell apoptosis and vasoconstriction.

OBJECTIVES

The aim of the study was to assess serum concentrations of VEGF and bFGF in the course of propranolol therapy of IH in children, and to assess their clinical implications.

MATERIAL AND METHODS

The study included 51 children with IH treated with propranolol. The participants were assessed before, during and after the therapy with Hemangioma Activity Score (HAS), Doppler ultrasound (US) of the lesions, as well as VEGF and bFGF serum concentrations.

RESULTS

All children showed clinical improvement measured in the HAS. A complete involution of the IH was reported in 32 (63%) children at the time of decision of the gradual withdrawing of propranolol, and in 28 (61%) patients at the end of the treatment (out of 46 patients present at the follow up after 1.5 months). Doppler US at the follow-up showed a complete disappearance of the blood flow in the lesion in 24 (52%) children and its reduction in 12 (26%) children. There was a significant decrease in VEGF and bFGF during and after treatment compared to pretreatment values. There was a correlation between the outcome of the Doppler US and changes in bFGF during and after treatment. Changes in VEGF during treatment did not correlate with changes in the Doppler US.

CONCLUSIONS

Serum concentrations of VEGF and bFGF decreased during the propranolol treatment of IH, which may indicate the effect of propranolol on both. However, the statistical analysis showed their low prognostic value as biochemical markers of propranolol treatment. Clinical evaluation combined with Doppler US is the most valuable method of monitoring the therapy.

摘要

背景

普萘洛尔已成为婴儿血管瘤(IH)的首选治疗药物。目前,人们对IH的发病机制以及普萘洛尔对其的作用机制了解尚浅。可能的解释包括通过降低血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF)来抑制血管生成、诱导血管内皮细胞凋亡以及血管收缩。

目的

本研究旨在评估儿童IH患者在普萘洛尔治疗过程中血清VEGF和bFGF的浓度,并评估其临床意义。

材料与方法

本研究纳入了51例接受普萘洛尔治疗的IH患儿。在治疗前、治疗期间和治疗后,采用血管瘤活动评分(HAS)、病变部位的多普勒超声(US)以及VEGF和bFGF血清浓度对参与者进行评估。

结果

所有患儿的HAS评分均显示临床症状改善。在决定逐渐停用普萘洛尔时,32例(63%)患儿的IH完全消退;在治疗结束时(1.5个月随访时的46例患者中),28例(61%)患者的IH完全消退。随访时的多普勒超声显示,24例(52%)患儿病变部位的血流完全消失,12例(26%)患儿的血流减少。与治疗前相比,治疗期间和治疗后VEGF和bFGF显著降低。治疗期间和治疗后,多普勒超声结果与bFGF的变化之间存在相关性。治疗期间VEGF的变化与多普勒超声的变化无相关性。

结论

在普萘洛尔治疗IH期间,血清VEGF和bFGF浓度降低,这可能表明普萘洛尔对两者均有作用。然而,统计分析显示,它们作为普萘洛尔治疗生化标志物的预后价值较低。临床评估结合多普勒超声是监测治疗最有价值的方法。

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