鼻息肉中的细胞因子研究进展

近年来细胞因子已成为研究鼻息肉病因的主导方向。本文就白细胞介素、胰岛素样生长因子、转化生长因子、血管内皮生长因子、细胞粘附分子的特点及在鼻息肉中的作用进行综述，发现所述因子在鼻息肉的发生发展中起着至关重要的作用。     

鼻息肉相关细胞因子的研究进展

近年来关于鼻息肉的发病机制研究较多,讨论的方向也较广,有关细胞因子在其中的作用逐渐成为主导研究方向,本文就血管内皮生长因子、白细胞介素5、转化生长因子β1、调节激活正常T细胞表达和分泌因子和基质金属蛋白酶的特点及其作用进行概述,以了解其在鼻息肉发生及发展过程中的重要作用。     

白细胞介素17与血管内皮生长因子在鼻息肉组织中的表达及相关性分析

目的　通过研究鼻息肉组织中白细胞介素17（interleukin 17,IL-17）和血管内皮生长因子（vascular endothelial growth factor,VEGF）的表达水平,探讨鼻息肉 的发生、发展。方法　收集在鼻内镜下慢性鼻-鼻窦炎伴鼻息肉手术患者鼻息肉组织30例,慢性鼻-鼻窦炎不伴鼻息肉手术患者筛窦黏膜组织30例,因鼻中隔偏曲行下鼻甲部分切除术患者下鼻甲黏膜组织10例。采用免疫组织化学SP法检测IL-17、VEGF的表达情况并对两者表达水平相关性进行分析。结果　IL-17、VEGF在鼻息肉组织中的表达明显高于其他两组,两两比较组间差异均具有统计学意义;IL-17与VEGF在鼻息肉组织中的表达呈正相关性。结论　IL-17和VEGF均在鼻息肉组织中的表达增高,对鼻息肉的发生、发展起重要作用;鼻息肉组织中IL-17与VEGF的表达呈正相关,提示两者共同参与鼻息肉的发生与发展。     

生长因子和细胞外基质在创伤修复过程中的作用

本文概括介绍了与创伤愈合有关的几种生长因子,包括血小板源性生长因子、成纤维细胞生长因子、表皮生长因子、转化生长因子、血管内皮生长因子、白细胞介素-1、白细胞介素-6和肿瘤坏死因子;以及参与创伤愈合的4种细胞外基质胶原蛋白、粘连糖蛋白、蛋白多糖和角质细胞胶原酶-1.初步阐明了这些创面愈合指标对鼻内镜手术术后的评估意义.     

生长因子和细胞外基质在创伤修复过程中的作用

本概括介绍了与创伤愈合有关的几种生长因子，包括血小板源性生长因子、成纤维细胞生长因子、表皮生长因子、转化生长因子、血管内皮生长因子、白细胞介素-1、白细胞介素-6和肿瘤坏死因子；以及参与创伤愈合的4种细胞外基质：胶原蛋白、粘连糖蛋白、蛋白多糖和角质细胞胶原酶-1。初步阐明了这些创面愈合指标对鼻内镜手术术后的评估意义。     

白细胞介素8及血管内皮生长因子在鼻息肉及鼻息肉病组织中的表达

鼻息肉及鼻息肉病可能是两种不同的疾病，且其发病机理迄今仍不清楚。为此，2002年4-10月，对在我院行鼻内镜手术的71例患者的标本，采用免疫组化方法检测白细胞介素-8（interleukin-8,IL-8）和血管内皮生长因子（vascular endothelial growth factor,VEGF）在其中的表达。     

血管内皮生长因子及其受体在鼻息肉中的表达

目的 :检测血管内皮生长因子及其受体在鼻息肉中的表达。方法 :将正常鼻粘膜和鼻息肉用 10 %福尔马林固定 ,石蜡包埋 ,切片。用免疫组织化学方法检测血管内皮生长因子及其受体在正常鼻粘膜和鼻息肉中的表达。结果 :血管内皮生长因子及其受体在正常鼻粘膜呈弱阳性 ,在鼻息肉呈强阳性表达。结论 :血管内皮生长因子在鼻息肉的形成中起重要作用。     

血管内皮生长因子及其受体在鼻息肉中的表达

目的：检测血管内皮生长因子及其受体在鼻息肉中的表达。方法：将正常鼻粘膜和鼻息肉用10％福尔马林固定，石蜡包埋，切片。用免疫组织化学方法检测血管内皮生长因子及其受体在正常鼻粘膜和鼻息肉中的表达。结果：血管内皮生长因子及其受体在正常鼻粘膜呈弱阳性，在鼻息肉呈强阳性表达。结论：血管内皮生长因子在鼻息肉的形成中起重要作用。     

白细胞介素35在鼻息肉中的作用机制

 鼻息肉是鼻腔、鼻窦黏膜的慢性炎症性疾病,其病因和发病机制尚不明确。研究认为鼻息肉的发生是多因素、多步骤的过程,其中多种炎症因子的表达和嗜酸性粒细胞的浸润是鼻息肉形成的最重要环节。目前在鼻息肉组织中发现调节性T细胞分泌不足,多种T细胞亚群Th1、Th2、 Th17分泌的促炎性因子高表达。已有研究表明白细胞介素35可通过促进调节性T细胞增殖,调节Th1/Th2细胞平衡,抑制Th17细胞的分化及其细胞因子的分泌等方面,影响疾病炎症过程,从而为鼻息肉的病因研究及治疗提供新的靶点。     

血管细胞上皮粘附因子—1、白细胞介素—8在鼻息肉中的检测及意义

目的 研究血管细胞上皮粘附因子-1（VCAM-1）、白细胞介素-8（IL-8）在鼻息肉发生机理中的意义。方法 38例病人经糖皮质激素局部治疗，用ELISA方法，检测VCAM-1及IL-8在鼻息肉中的表达，结果 嗜酸性粒细胞个数与鼻腔分泌物中IL-8水平有一定的相关性，VCAM-1的表达有显著差异，结论 表明VCAM-1与IL-8参与了水肿型鼻息肉的发生，为进一步揭示其发生机理提供依据。     

Immunohistochemical expression of VEGF and VEGF receptors in nasal polyps as compared to normal turbinate mucosa

The factors involved in the development of chronic inflammation and edema in nasal polyps remain to be clarified. The expression of vascular endothelial growth factor (VEGF) has been described in plasma cells, suggesting that plasma cells may play a major role in the development of edema in nasal polyps through the production of VEGF. We performed immunohistochemical analysis using specific antibodies to VEGF and to the known VEGF receptors, VEGFR-1 and VEGFR-2, on paraffin sections of human nasal polyps ( n=11) and controls of human mucosa of the normal middle turbinates ( n=6). In normal turbinate mucosa, sporadic immunostaining for VEGF was observed throughout the endothelial cells of the small veins and arteries. VEGFR-1 and VEGFR-2 expression was faint in the healthy turbinates. In nasal polyp tissues, strong immunostaining for VEGF was found in the endothelium of blood vessels and in the infiltrating perivascular inflammatory cells. Fibroblasts also stained for VEGF. Strong immunolabeling to VEGFR-1 was evident in the vascular endothelium, whereas weak to moderate VEGFR-1-staining was generally confined to scattered mononuclear round cells. Mononuclear round cells and the endothelium of capillaries revealed immunoreactivity to VEGFR-2. These findings support a role for VEGF and its receptors, VEGFR-1 and VEGFR-2, in the development and perpetuation of edema and angiogenesis in nasal polyps.     

Expression, localization, and significance of vascular permeability/vascular endothelial growth factor in nasal polyps

BACKGROUND: The exact etiologic mechanisms leading to the formation of nasal polyps have remained largely obscure. A key phenomenon of this specific type of chronic inflammatory disease in nasal respiratory mucosa is remarkable edema. Vascular permeability/vascular endothelial growth factor (VPF/VEGF) plays an important role in inducing angiogenesis and modulating capillary permeability. OBJECTIVE: To study the expression and localization of VPF/ VEGF as a putative key factor in nasal polyp development. METHODS: Specimens of nasal polyps (n = 12) were harvested during endonasal sinus surgery in patients with polypous chronic rhinosinusitis. Specimens of healthy nasal respiratory mucosa (n = 12) served as controls and were obtained from inferior turbinates of patients undergoing surgery for nasal obstruction without signs and symptoms of inflammatory disease. Frozen sections were immunohistochemically stained for VPF/VEGF and quantitatively analyzed, using computer-based image analysis. RESULTS: The expression of VPF/VEGF in specimens of nasal polyps was significantly stronger than in specimens of healthy nasal mucosa of controls. VPF/VEGF in polypous tissue was mainly localized in vascular endothelial cells, in basal membranes and perivascular spaces, and in epithelial cells. CONCLUSION: The markedly increased expression in nasal polyps as opposed to healthy nasal mucosa suggests that VPF/VEGF may play a significant role in both the formation of nasal polyps and in the induction of heavy tissue edema. This finding is discussed with respect to the differential expression of cyclooxygenase (COX) isoenzymes-1 and -2 (COX-1 and COX-2) in nasal polyps was significantly stronger than in specimens of healthy nasal mucosa of controls. VPF/VEGF in polypous tissue was mainly localized in vascular endothelial cells, in basal membranes and perivascular spaces, and in epithelial cells. Conclusion: The markedly increased expression in nasal polyps as opposed to healthy nasal mucosa suggests that VPF/VEGF may play a significant role in both the formation of nasal polyps and in the induction of heavy tissue edema. This finding is discussed with respect to the differential expression of cyclooxygenase (COX) isoenzymes-1 and -2 (COX-1 and COX-2) in nasal polyps.     

血管内皮生长因子在鼻息肉组织中的表达和意义

目的探讨血管内皮生长因子(vascular endothelial growth factor, VEGF)在鼻息肉组织中的表达及其在鼻息肉发病中的意义。方法将鼻息肉患者分为A、B 组,A组为Ⅱ型1、2期患者,B组为Ⅱ型3期及Ⅲ型患者。另有20例鼻中隔偏曲患者的正常下鼻甲组织作对照组。采用免疫组化SP法检测三组VEGF的表达。结果正常鼻黏膜中VEGF的染色呈弱阳性,而在A、B组鼻息肉组织中VEGF的阳性率明显高于对照组,B组中阳性率和阳性细胞数均高于A组;VEGF在鼻息肉组织中主要定位于基底膜周围的炎性细胞和上皮细胞以及腺体、血管周围和血管壁内皮细胞。结论VEGF通过在鼻息肉组织中过度表达促进息肉组织内的血管增殖和炎性细胞聚积,促进鼻息肉的发生发展。     

Vascular endothelial growth factor and children featuring nasal polyps

BACKGROUND: The aim of this study is to explore the expression of vascular endothelial growth factor within nasal polyps, and the implication of such expression as regards the development of nasal polyps amongst children. MATERIAL AND METHODS: Sixty children suffering from chronic rhinosinusitis were enrolled in this study. Amongst them, 30 patients featured rhinosinusitis with associated nasal polyps. A biopsy specimen was taken from the stalk or the base of the nasal polyp for nasal-polyp sufferers, and the ethmoid sinus for study participants who featured no nasal polyps. The primary lesions biopsied were immunohistochemically stained with a specific endothelial-cell marker and also stained for the presence of vascular endothelial growth factor. The specific level of vascular endothelial growth factor and the mean number of blood vessels present in a visual microscopic (biopsied-specimen) field were calculated under light microscopy (x400). RESULTS: The number of vascular endothelial growth factor-expressing cells for the nasal-polyp group and for the sinusitis group was, respectively, 20.8+/-4.0 and 11.5+/-3.4 per visual field. Correspondingly, the mean intra-polyp blood-vessel density for the nasal-polyp group and that for the control group was, respectively, 10.5+/-2.6 and 5.0+/-1.9 per visual field. The mean intra-polyp blood-vessel density and the number of vascular endothelial growth factor-expressing cells proved to be significantly greater amongst individuals from the nasal-polyp group than was the case for their analogs from the sinusitis group (P<0.01, for both). The presence of vascular endothelial growth factor was found to be distributed predominantly within the vascular endothelium and the mast cells of polyp tissue. In addition, the level of vascular endothelial growth-factor expression and the mean blood-vessel count per field correlated significantly for nasal-polyp tissue (P<0.001). Furthermore, the relative size of nasal polyps correlated significantly with the number of (intra-polyp) vascular endothelial-cell growth factor-expressing cells and the mean blood-vessel density (P<0.05, for both). CONCLUSION: The level of expression of vascular endothelial-cell growth factor (VEGF) and the mean blood-vessel density were shown to be significantly greater within nasal polyps than within corresponding sinusitis mucosa. Clinically, the expression of both of these parameters correlated well with the relative size of nasal polyps. Vascular endothelial growth factor participates in the formation of nasal polyps amongst children suffering from chronic rhinosinusitis (CRS).     

黏附分子及血管内皮生长因子在鼻息肉中的表达

目的 探讨细胞间黏附分子-1（ICAM-1）、血管细胞黏附分子-1（VCAM-1）以及血管内皮生长因子（VEGF）在鼻息肉中的表达与意义。方法25例鼻息肉标本和9例下鼻甲黏膜标本，分别行ICAM-1、VCAM-1、VEGF免疫组化染色和HE染色，光镜下观察比较各种分子表达水平。结果 鼻息肉中可见大量嗜酸性粒细胞（EOS）浸润。ICAM-1、VCAM-1和VEGF均可表达于鼻息肉血管内皮、间质及炎症细胞，且在鼻息肉血管内皮、间质及浸润炎症细胞中的表达趋势呈现正相关关系。结论 ICAM-1、VCAM-1可能与EOS等炎症细胞附壁浸润活化过程关系密切，VEGF可能启动并加强这一病理变化。它们的协同作用可能参与了鼻息肉的病理过程。     

Expression of vascular endothelial growth factor and transforming growth factor-beta 1 in nasal polyps]

OBJECTIVE: To study the expression and significance of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) and transforming growth factor-beta 1(TGF-beta 1) in nasal polyps. METHODS: Expression of VEGF/VPF and TGF-beta 1 in nasal polyps from 34 patients and middle turbinates from 30 patients with deviation of nasal septum was prospectively studied with immunohistochemistry. Tissue sections were observed under optical microscope. RESULTS: (1) The VEGF/VPF positivity in vascular endothelium and in glandular cell was significantly higher in nasal polyps than in middle turbinates (P < 0.01 and P < 0.05, respectively); (2) The TGF-beta 1 positivity in extracellular matrix and in cells in the stroma was significantly higher in nasal polyps than in middle turbinates(P < 0.005); (3) The distribution and shape of TGF-beta 1 expressing cells in nasal polyps were similar to that of eosinophil, their positivities were significantly correlative; (4) The positivity of VEGF/VPF and TGF-beta 1 did not correlate with clinical type in nasal polyps (P > 0.05). CONCLUSION: (1) The VEGF/VPF may play a key role in the formation of heavy edema of nasal polyps; (2) The TGF-beta 1 may contribute to some of the pathologic changes observed in nasal polyps, such as thickening of the epithelial basement membrane and stromal fibrosis; (3) Eosinophils in nasal polyps represent a major source of TGF-beta 1.     

鼻息肉中血管内皮生长因子mRNA的检测与意义

目的 :检测鼻息肉组织和鼾症下鼻甲粘膜组织中的血管内皮生长因子 (VEGF) m RN A水平的表达 ,了解其在慢性炎症过程中的作用。方法 :取 6例行下鼻甲切除术的下鼻甲粘膜和 7例鼻息肉切除术的鼻息肉标本 ,用半定量的反转录 -聚合酶链反应 (RT- PCR)方法检测 VEGF的 m RNA表达。结果 :RT- PCR结果显示在鼻息肉组织中 V EGF的表达较鼾症患者下鼻甲粘膜组织明显升高。结论 :鼻息肉组织中 VEGF的表达显著升高 ,推测 VEGF在鼻息肉的形成、生长及复发过程中具有极其重要的作用。     

Vascular endothelial growth factor in nasal polyps: a comparison of asthmatic and non-asthmatic patients

The cause of nasal polyps remains unknown, although there is a well-recognized clinical association between nasal polyposis and asthma. The characteristic histological features of nasal polyps include large quantities of extracellular fluid. Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis and vascular permeability. This study aimed to compare expression of VEGF in nasal polyps from patients with asthma and those with no apparent respiratory disease. Twenty-four asthmatic and 35 non-asthmatic patients were studied using immunohistochemistry for VEGF. VEGF expression was identified in endothelial, inflammatory and epithelial cells. There was significantly greater endothelial expression of VEGF in asthmatic patients (P < 0.05). Greater epithelial expression was observed in asthmatic patients but this did not reach statistical significance (P = 0.07). There was no difference in the density of inflammatory cells expressing VEGF. Differences between the two groups may reflect differences in disease severity or in the nature of the inflammatory process.     

Vascular endothelial growth factor in nasal polyps: a comparison of asthmatic and non‐asthmatic patients

The cause of nasal polyps remains unknown, although there is a well‐recognized clinical association between nasal polyposis and asthma. The characteristic histological features of nasal polyps include large quantities of extracellular fluid. Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis and vascular permeability. This study aimed to compare expression of VEGF in nasal polyps from patients with asthma and those with no apparent respiratory disease. Twenty‐four asthmatic and 35 non‐asthmatic patients were studied using immunohistochemistry for VEGF. VEGF expression was identified in endothelial, inflammatory and epithelial cells. There was significantly greater endothelial expression of VEGF in asthmatic patients (P < 0.05). Greater epithelial expression was observed in asthmatic patients but this did not reach statistical significance (P = 0.07). There was no difference in the density of inflammatory cells expressing VEGF. Differences between the two groups may reflect differences in disease severity or in the nature of the inflammatory process.     

Immunohistochemical demonstration and semi-quantitation of vascular endothelial growth factor in recurrent versus non-recurrent nasal polyps

OBJECTIVE: The expression of some growth factors in nasal polyps has been examined, although investigations addressing the reason for recurrence in some patients are lacking. Vascular endothelial growth factor (VEGF) is expressed by inflammatory cells, as well as by endothelial and epithelial cells of nasal polyps. To determine whether VEGF may play a role in the recurrence of nasal polyps, we aimed to compare VEGF expression in recurrent versus non-recurrent polyps. In addition, expression in polyps from asthmatic patients was compared with that in polyps from non-asthmatics. MATERIAL AND METHODS: A total of 30 patients with newly diagnosed nasal polyposis were included. Polypectomy was performed at enrolment in the long-term follow-up study. Fifteen patients had only 1 polypectomy (non-recurrence group; median observation period 81 months) and 15 had a median of 6.4 polypectomies (multiple recurrence group; median observation period 108 months). Five of 10 patients with asthma belonged to the non-recurrence group and 5 to the recurrence group. The polyp obtained at the initial polypectomy was examined for expression of VEGF by immunohistochemistry, using a polyclonal antibody. A blinded semi-quantitation and comparison of the intensity of immunolabelling were performed in recurrent versus non-recurrent polyps, as well as in asthmatics versus non-asthmatics. RESULTS: VEGF expression was seen as varying staining of the polyp surface and gland epithelium, as well as of the vessel endothelium and some stromal mono- and polymorphonuclear leukocytes. Semi-quantitation of the staining intensity showed no significant differences between recurrent and non-recurrent polyps, or between asthmatics and non-asthmatics. CONCLUSION: Our findings indicate that the level of immunohistochemical expression of VEGF in recurrent and nonrecurrent nasal polyposis is equivalent. Thus, the level of VEGF expression cannot predict a subsequent recurrence. The expression of VEGF is not upregulated in patients with asthma. Further studies are needed to determine the role of VEGF in nasal polyposis, with special reference to different stages of polyp formation, vascularization and growth.