Chae Sung Won, Kim Seo Jin, Kim Jeung Lim, Jung Hak Hyun
Department of Otolaryngology--Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea.
Acta Otolaryngol. 2003 Jun;123(5):559-63. doi: 10.1080/00016480310001501.
Increased vascular permeability and endothelial cell growth are important in the pathogenesis of otitis media with effusion (OME) and vascular endothelial growth factor (VEGF) is known to play an important role in the increased vascular permeability and angiogenesis associated with OME. The action of VEGF is mediated by two different high-affinity receptors--VEGF receptor-1 (VEGFR-1; flm-like tyrosine kinase-1; flt-1) and VEGFR-2 (kinase insert domain-containing receptor; flk-1)--predominantly located on the vascular endothelium. The purpose of this study was to investigate the expression of three forms of VEGFR (-1, -2 and -3) in an endotoxin-induced rat model of OME.
Middle ear mucosa were obtained at 0, 1, 3, 6 and 12 h and 1, 3, 7 and 14 days after induction, and the expression of VEGFR mRNA and protein was evaluated using semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting.
RT-PCR revealed that the expression of VEGFR-1 and -2 mRNA was upregulated between 1 h and 3 days after endotoxin instillation, with peak expression occurring at 12 h and on Day 1. No expression of VEGFR-3 mRNA was detected in any of the samples. Expression patterns of VEGFR-1 and -2 protein observed by Western blotting were similar to those of VEGFR-1 and -2 mRNA and peak expression was observed on Day 1. Expression of VEGFR mRNA or protein was not detected in either normal or saline-instilled middle ear mucosa.
These results suggest that both VEGFR-1 and -2 are upregulated during experimental otitis media in the rat and these receptors may play different roles in the production of effusion in OME.
血管通透性增加和内皮细胞生长在分泌性中耳炎（OME）的发病机制中起重要作用，已知血管内皮生长因子（VEGF）在与OME相关的血管通透性增加和血管生成中起重要作用。VEGF的作用由两种不同的高亲和力受体介导——VEGF受体-1（VEGFR-1；类fms样酪氨酸激酶-1；flt-1）和VEGFR-2（含激酶插入结构域的受体；flk-1），主要位于血管内皮。本研究的目的是调查三种形式的VEGFR（-1、-2和-3）在内毒素诱导的大鼠OME模型中的表达。
在诱导后0、1、3、6和12小时以及1、3、7和14天获取中耳黏膜，使用半定量逆转录聚合酶链反应（RT-PCR）和蛋白质印迹法评估VEGFR mRNA和蛋白质的表达。
RT-PCR显示，在内毒素滴注后1小时至3天，VEGFR-1和-2 mRNA的表达上调，在12小时和第1天出现峰值表达。在任何样本中均未检测到VEGFR-3 mRNA的表达。蛋白质印迹法观察到的VEGFR-1和-2蛋白质的表达模式与VEGFR-1和-2 mRNA的相似，在第1天观察到峰值表达。在正常或生理盐水滴注的中耳黏膜中均未检测到VEGFR mRNA或蛋白质的表达。
这些结果表明，在大鼠实验性中耳炎期间，VEGFR-1和-2均上调，并且这些受体可能在OME积液的产生中发挥不同作用。
