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暴露26年后对硫芥中毒受试者血管生成细胞因子与角膜新生血管形成之间关联的研究

Investigating the Association between Angiogenic Cytokines and Corneal Neovascularization in Sulfur Mustard Intoxicated Subjects 26 Years after Exposure.

作者信息

Abbaszadeh Mohammad, Aidenloo Naser Samadi, Nematollahi Mohammad Karim, Motarjemizadeh Qader

机构信息

Department of Ophthalmology, Medical University of Urmia, Urmia, Iran.

Department of Ophthalmology, Aja University of Medical Sciences, Tehran, Iran.

出版信息

Toxicol Int. 2014 Sep-Dec;21(3):300-6. doi: 10.4103/0971-6580.155375.

Abstract

OBJECTIVES

This study aimed to evaluate the associations between the concentrations of three major angiogenic cytokines-vascular endothelial growth factor-A165 (VEGF-A165), basic fibroblast growth factor (bFGF), and platelet-derived growth factor-BB (PDGF-BB)-in the tear of sulfur mustard (SM)-exposed subjects and corneal neovascularization (CNV) 26 years after exposure.

MATERIALS AND METHODS

The concentrations of VEGF-A, bFGF, and PDGF-BB were measured by enzyme-linked immunosorbent assay (ELISA) in reflex tears of (i) SM-injured patients with CNV (positive case group including 18 individuals) and (ii) SM-injured patients without CNV (negative case group including 22 individuals). Then results were compared to corresponding values obtained from tears of 40 healthy control subjects.

RESULTS

The mean concentrations of all investigated growth factors, VEGF-A165, bFGF, and PDGF-BB, were significantly higher in positive cases than controls (P ≤ 0.001, P = 0.028, and P = 0.041, respectively). Whereas, VEGF-A165 was the only growth factor which displayed significantly elevated concentrations in negative case group compared to the healthy individuals (P = 0.030). Additionally, the mean level of VEGF-A165 was also higher in positive patient group than negative patients (P = 0.022). Subjects with increased concentrations of tear VEGF-A165 were more than 10 times more likely to suffer from CNV than normal individuals (odds ratio (OR) = 10.43, confidence interval (CI): 2.14-38.46, P = 0.001), while elevated levels of bFGF and PDGF-BB increased the risk of CNV by about twofold.

CONCLUSION

Although all investigated cytokines had increased in tears of positive patients, VEGF-A was the only one which showed a significant correlation with the severity of CNV, and thus played a crucial role in corneal angiogenesis.

摘要

目的

本研究旨在评估硫芥(SM)暴露受试者泪液中三种主要血管生成细胞因子——血管内皮生长因子-A165(VEGF-A165)、碱性成纤维细胞生长因子(bFGF)和血小板衍生生长因子-BB(PDGF-BB)的浓度与暴露26年后角膜新生血管形成(CNV)之间的关联。

材料与方法

通过酶联免疫吸附测定(ELISA)测量(i)患有CNV的SM损伤患者(阳性病例组,包括18名个体)和(ii)未患有CNV的SM损伤患者(阴性病例组,包括22名个体)反射性泪液中VEGF-A、bFGF和PDGF-BB的浓度。然后将结果与40名健康对照受试者泪液中的相应值进行比较。

结果

所有研究的生长因子,即VEGF-A165、bFGF和PDGF-BB,在阳性病例中的平均浓度均显著高于对照组(分别为P≤0.001、P = 0.028和P = 0.041)。然而,与健康个体相比,VEGF-A165是阴性病例组中唯一浓度显著升高的生长因子(P = 0.030)。此外,阳性患者组中VEGF-A165的平均水平也高于阴性患者(P = 0.022)。泪液中VEGF-A165浓度升高的受试者患CNV的可能性是正常个体的10倍以上(优势比(OR)= 10.43,置信区间(CI):2.14 - 38.46,P = 0.001),而bFGF和PDGF-BB水平升高使CNV风险增加约两倍。

结论

尽管所有研究的细胞因子在阳性患者的泪液中均有所增加,但VEGF-A是唯一与CNV严重程度呈显著相关的因子,因此在角膜血管生成中起关键作用。

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