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Vascular endotherial growth factor )VEGF) in paranasal sinusitis and allergic rhinitis

血管内皮生长因子 (VEGF) 在鼻窦炎和过敏性鼻炎中的作用

基本信息

批准号：
11671694
负责人：
MATSUNE Shoji
金额：
$ 2.18万
依托单位：
Kagoshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

The level of Vascular Endothelial Growth Factor (VEGF) in nasal secretions and blood plasma obtained from rhinosinusitis cases was quantified by enzyme-linked immunosorbent assay (ELISA) and compared among patients with nasal allergy and those with paranasal sinusitis with/without nasal allergy. In addition, the distribution of VEGF-positive cells in paranasal sinus mucosa obtained during surgical procedures was investigated immunohistochemincally. The ratio of VEGF to albumin (V/A) in nasal secretion was significantly higher than that of VEGF in plasma (p,0.01) in all the rhinosinusitis cases. Among rhinosinusitis cases, the ratio of V/A in nasal secretion was higher in cases of nasal allergy (p<0.01) or sinusitis with nasal allergy (p<0.02) than in cases with sinusitis only. According to the immunohistochemical study, VEGF-positive findings were observed in inflammatory infiltrating cells including eosinophils, serous glandular acini and vascular endothelium. While glandular acini clearly differentiating to the serous or mucous type were observed to be hyperplastic in allergic cases, hyperplastic glandular acini were not clearly differentiating to the serous or mucous type in non-allergic cases. These results suggest that VEGF production increases at the site of rhinosinusitis mucosa especially in cases with allergic diseases. According to the study by cultured fibloblasts from human nasal polyp, VEGF production was activated by hypoxia and it was suppressed by clarithromycin (CAM), roxithromycin (RXM) and Dexametazone (DXM) but not by Ampicillin (ABPC) and Dimethyl Sulfoxide (DMSO). PD098059 suppressed more effectively the VEGF production from the culture under hypoxia than Gliotoxin, which suggests the pathway of tyrosine phosphorylation of Mitogen-Activated Protein (MAP) kinase is more important than that of Nuclear Factor κ B (NFκB) under the hypoxic stress on nasal fibloblasts.

采用酶联免疫吸附试验（ELISA）检测鼻窦炎患者鼻分泌物和血浆中血管内皮生长因子（VEGF）的水平，并比较鼻变态反应患者和伴或不伴鼻变态反应的副鼻窦炎患者的VEGF水平。此外，VEGF阳性细胞的分布，在手术过程中获得的鼻窦粘膜进行了化学研究。鼻窦炎患者鼻分泌物中VEGF与白蛋白的比值（V/A）明显高于血浆中VEGF（P < 0.01）。鼻窦炎患者鼻分泌物中V/A比值在鼻变态反应组（P<0.01）和鼻窦炎合并鼻变态反应组（P<0.02）明显高于单纯鼻窦炎组（P<0.01）。免疫组化结果显示，VEGF在炎性浸润细胞，包括嗜酸性粒细胞、浆液腺泡和血管内皮细胞中呈阳性表达。虽然在过敏病例中观察到明显分化为浆液性或粘液性的腺泡是增生的，但在非过敏病例中增生的腺泡没有明显分化为浆液性或粘液性。这些结果表明，血管内皮生长因子的生产增加的网站鼻窦炎粘膜，特别是在案件过敏性疾病。用培养的人鼻息肉成纤维细胞研究发现，缺氧可激活VEGF的生成，克拉霉素（CAM）、罗红霉素（RXM）和地塞米松（DXM）可抑制VEGF的生成，而氨苄青霉素（ABPC）和二甲基亚砜（DMSO）则不抑制VEGF的生成。PD 098059对缺氧条件下培养的鼻成纤维细胞VEGF的抑制作用强于Gliotoxin，提示在鼻成纤维细胞缺氧应激过程中，丝裂原活化蛋白（MAP）激酶的酪氨酸磷酸化途径比核因子κ B（NFκB）的酪氨酸磷酸化途径更为重要。