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

采用双抗体夹心酶联免疫吸附试验(EL ISA)检测鼻窦炎患者鼻腔分泌物和血浆中血管内皮生长因子(VEGF)的水平，并比较鼻变态反应与副鼻窦炎伴或不伴鼻变态反应者之间的差异。此外，应用免疫组织化学方法研究了手术过程中获取的鼻窦粘膜中血管内皮生长因子阳性细胞的分布。鼻窦炎患者鼻腔分泌物中的血管内皮生长因子与白蛋白的比值(V/A)显著高于血浆中的血管内皮生长因子(P<0.01)。在鼻窦炎患者中，鼻变态反应组(P&lt；0.01)或鼻窦炎伴鼻变态反应组(P&lt；0.02)的鼻分泌物中V/A值高于单纯鼻窦炎组。免疫组织化学染色显示，血管内皮生长因子阳性的炎性细胞包括嗜酸性粒细胞、浆液性腺泡和血管内皮细胞。变态反应性腺泡明显分化为浆液型或粘液型，而非变态反应性腺泡不明显分化为浆液型或粘液型。这些结果表明，在鼻窦炎黏膜部位，尤其是在变态反应性疾病的病例中，血管内皮生长因子的产生增加。体外培养的人鼻息肉成纤维细胞的研究表明，低氧可激活血管内皮生长因子的产生，克拉霉素(CAM)、罗红霉素(RXM)和地塞米松(DXM)可抑制其产生，而氨苄西林(ABPC)和二甲基亚砜(DMSO)则不能抑制其产生。PD098059对低氧条件下培养的鼻成纤维细胞产生血管内皮生长因子的抑制作用强于低氧毒素，提示在低氧应激条件下，丝裂原活化蛋白(MAP)激酶的酪氨酸磷酸化途径比核因子κB(NFκB)途径更为重要。

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.